Mehnaaz S. Khuroo

Molecular adsorbent recirculating system for acute and acute‐on‐chronic liver failure: A meta‐analysis

Molecular adsorbent recirculating system (MARS) is an important option for patients with liver failure to give them additional time for recovery or to serve as a “bridge” to transplantation. However, its effect on survival for such patients is not well known. Our aim was to assess the treatment effects of MARS on patients with acute and acute‐on‐chronic liver failure. The outcomes measure evaluated was survival. We searched Medline (1966–2002) and EMBASE (1974–2002) using the terms liver failure, liver support systems, and MARS. Our search was extended to the Cochrane Controlled Trials Registry Database, published abstracts from 5 international conferences, Teraklin (the manufacturer of MARS), known contacts, and bibliographies from each full‐published report. We included trials published in English and non‐English languages. Eligible studies were randomized and nonrandomized controlled trials, which compared the treatment effects of MARS with standard medical treatment. Of the 206 articles screened, 4 randomized controlled trials including 67 patients were analyzed. Two nonrandomized trials with 61 patients were used for explorative analysis. The methodology, population, intervention, and outcomes of each selected trial were evaluated by duplicate independent review. Disagreements were resolved by consensus. In the primary meta‐analysis, MARS treatment did not appear to reduce mortality significantly compared with standard medical treatment [relative risk (RR), 0.56; 95% confidence interval (CI), 0.28–1.14; P = .11]. Only 1 of the 4 randomized trials analyzed showed significant reduction in mortality. Sensitivity analysis of 3 peer‐reviewed trials did not reduce mortality significantly with MARS treatment (RR, 0.72; 95% CI, 0.37–1.40; P = .33). Subgroup analysis of 2 trials for acute liver failure and another 2 trails for acute‐on‐chronic liver failure also did not reveal any benefit to survival with MARS treatment. In contrast, explorative analysis of 2 nonrandomized trials showed a significant survival benefit with MARS treatment (RR, 0.36; 95% CI, 0.17–0.76; P = .007). This was possibly related to bias in the selection of patients in the nonrandomized trials. In conclusion, MARS treatment had no significant survival benefit on patients with liver failure when compared with standard medical therapy. However, we found only a few trials with a small number of patients for the analysis, allowing for the possibility of false negative and erroneous conclusions. Well‐conducted randomized trials are strongly recommended to define the role of MARS in the treatment of patients with liver failure. (Liver Transpl 2004;10:1099–1106.)

Treatment with proton pump inhibitors in acute non‐variceal upper gastrointestinal bleeding: A meta‐analysis

Medical therapy is an attractive adjuvant to endoscopic treatment in upper gastrointestinal (UGI) bleeding. This review aims to assess the treatment effects of proton pump inhibitor (PPI) therapy in acute non‐variceal UGI bleeding. Outcome measures evaluated were further bleeding, surgery, all‐cause deaths, ulcer deaths and non‐ulcer deaths. We searched MEDLINE (1966–2002) and EMBASE (1974–2002) using the terms ‘gastrointestinal hemorrhage’, ‘peptic ulcer hemorrhage’, ‘proton pump inhibitor’, ‘omeprazole’, ‘pantoprazole’, ‘lansoprazole’, ‘rabeprazole’ and ‘esomeprazole’. The search was extended to the Cochrane controlled trials registry database, published abstracts from five international gastroenterology conferences, manufacturers of PPI, known contacts and bibliographies from each full‐length published report. We included trials published in English and non‐English languages. Eligible studies were randomized controlled trials that compared the treatment effects of PPI therapy with placebo or H2 receptor antagonists in patients with acute non‐variceal UGI bleeding. Of the 175 articles screened, 26 controlled trials including 4670 subjects (2317 in treatment arm and 2353 in control arm) were analyzed. The methodology, population, intervention, and outcomes of each selected trial were evaluated using duplicate independent review. Disagreements were resolved by consensus. PPI therapy significantly reduced rates of further bleeding (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40–0.57) and surgery (OR, 0.61; 95% CI, 0.48–0.76). All‐cause deaths were unaffected (OR, 1.02; 95% CI, 0.76–1.37). Ulcer deaths showed a significant reduction (OR, 0.58; 95% CI, 0.35–0.96), while non‐ulcer deaths showed a significant increase (OR, 1.60; 95% CI, 1.06–2.41) in the PPI therapy group. Sensitivity analysis of 22 trials published in peer‐reviewed journals, 10 trials with double‐blind design and 19 trials with high quality score and 22 trials using omeprazole in the treatment group showed results similar to those seen in the analysis of all 26 trials, confirming the stability of the conclusions. Subgroup analysis revealed that summary outcome measures were not influenced by control group therapy (placebo vs H2 receptor antagonists) or the use of prior endoscopic treatment to achieve hemostasis (given vs not given). However, the summary treatment effects for further bleeding and need for surgery were significant in only those trials enrolling patients with peptic ulcers having high risk for rebleeding and not in those trials enrolling patients with all causes of UGI bleeding. The summary treatment effects for further bleeding and need for surgery were significant in trials using intravenous as well as oral PPI. However, summary OR for all‐cause deaths and non‐ulcer deaths in trials using intravenous PPI were higher in the treatment group and not in trials using oral PPI. This raised the possibility of intravenous PPI‐therapy‐associated non‐ulcer deaths in high‐risk patients. PPI therapy in acute non‐variceal UGI bleeding reduced rates of further bleeding, surgery and deaths caused by ulcer complications. However, non‐ulcer deaths were increased. The overall mortality was unaffected. PPI therapy is useful only in a selected group of patients with acute non‐variceal UGI bleeding, namely those with peptic ulcers having endoscopic high‐risk stigmata for rebleeding.

Hepatitis E: an emerging global disease – from discovery towards control and cure

Hepatitis E is a systemic disease affecting the liver predominantly and caused by infection with the hepatitis E virus (HEV). HEV has marked genetic heterogeneity and is known to infect several animal species including pigs, boar, deer, mongoose, rabbit, camel, chicken, rats, ferret, bats and cutthroat trout. HEV is the sole member of the family Hepeviridae and has been divided into 2 genera: Orthohepevirus (mammalian and avian HEV) and Piscihepevirus (trout HEV). Human HEVs included within the genus Orthohepevirus are designated Orthohepevirus A (isolates from human, pig, wild boar, deer, mongoose, rabbit and camel). Hepatitis E is an important public health concern, and an estimated one‐third of the world population has been infected with HEV. In recent years, autochthonous hepatitis E is recognized as a clinical problem in industrialized countries. Several animal species especially domestic swine, wild boar and wild deer are reservoirs of genotype HEV‐3 and HEV‐4 in these countries. Human infections occur through intake of uncooked or undercooked meat of the infected animals and pig livers or sausages made from these livers and sold in supermarkets. HEV can be transmitted through blood and blood component transfusions, and donor screening for HEV is under serious consideration. Chronic hepatitis E resulting in rapidly progressive liver cirrhosis and end‐stage liver disease has been described in organ transplant patients. Ribavirin monotherapy attains sustained virological response in most patients. HEV 239 vaccine has been marketed in China and its long‐term efficacy over four and a half years reported.

Hepatitis E: Discovery, global impact, control and cure

Hepatitis E was identified as an epidemic of non-A, non-B hepatitis from Kashmir, India in 1978. Hepatitis E virus (HEV), the etiological agent is the sole member of family Hepeviridae. The virus has marked heterogeneity and infects many animals like bats, camel, chicken, deer, boar, mongoose, pigs, rats, rabbit and cutthroat trout. Hepatitis E is a disease with a major global impact and has two distinct epidemiological patterns. Hepatitis E is an imperative health issue in developing nations, transmitted through sullied water and happens most every now in young adults. The disease is particularly severe during pregnancy and in people with underlying liver cirrhosis. Autochthonous hepatitis E is increasingly recognized in developed countries. The virus infects domestic pigs, wild boar and Sika deer in these countries. HEV infections in humans occur by eating the undercooked game flesh, raw liver from supermarkets and Figatelli sausages. Blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is under consideration. Hepatitis E causes a number of extrahepatic diseases, including a wide spectrum of neurological syndromes. HEV genotype 3 causes prolonged viremia, chronic hepatitis, liver fibrosis and cirrhosis in organ transplant patients. The virus is amenable to ribavirin monotherapy and most patients clear the virus in a few weeks. Hepatitis E vaccine -239, marketed in China, has shown high efficacy with sustained protection for over four years.

Transmission of Hepatitis E Virus in Developing Countries

Hepatitis E virus (HEV), an RNA virus of the Hepeviridae family, has marked heterogeneity. While all five HEV genotypes can cause human infections, genotypes HEV-1 and -2 infect humans alone, genotypes HEV-3 and -4 primarily infect pigs, boars and deer, and genotype HEV-7 primarily infects dromedaries. The global distribution of HEV has distinct epidemiological patterns based on ecology and socioeconomic factors. In resource-poor countries, disease presents as large-scale waterborne epidemics, and few epidemics have spread through person-to-person contact; however, endemic diseases within these countries can potentially spread through person-to-person contact or fecally contaminated water and foods. Vertical transmission of HEV from infected mother to fetus causes high fetal and perinatal mortality. Other means of transmission, such as zoonotic transmission, can fluctuate depending upon the region and strain of the virus. For instance, zoonotic transmission can sometimes play an insignificant role in human infections, such as in India, where human and pig HEV infections are unrelated. However, recently China and Southeast Asia have experienced a zoonotic spread of HEV-4 from pigs to humans and this has become the dominant mode of transmission of hepatitis E in eastern China. Zoonotic HEV infections in humans occur by eating undercooked pig flesh, raw liver, and sausages; through vocational contact; or via pig slurry, which leads to environmental contamination of agricultural products and seafood. Lastly, blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is currently under serious consideration. To summarize, HEV genotypes 1 and 2 cause epidemic and endemic diseases in resource poor countries, primarily spreading through contaminated drinking water. HEV genotypes 3 and 4 on the other hand, cause autochthonous infections in developed, and many developing countries, by means of a unique zoonotic food-borne transmission.

Trichuris dysentery syndrome: a common cause of chronic iron deficiency anemia in adults in an endemic area (with videos)

BACKGROUND There are few published reports of Trichuris dysentery syndrome (TDS) in children. The disease has not been reported in adults. OBJECTIVE To report the clinical, colonoscopic, and histologic findings of TDS in adults in an endemic area. DESIGN Case series. SETTING Tertiary gastroenterology center. PATIENTS Eighty-four consecutive adult patients with chronic iron deficiency anemia over a 3-year period were investigated. Ten patients had severe Trichuris trichiura infection and received a diagnosis of TDS. INTERVENTIONS AND MAIN OUTCOME MEASUREMENTS Colonoscopy and colonic biopsies. Patients received anthelmintic treatment, and their response was assessed. RESULTS Ten patients with TDS were studied, including 8 female and 2 male patients with a mean (+/- standard deviation) age of 43 (+/- 15.5) years (range 15-65 years) and a hemoglobin level (+/- standard deviation) of 6.0 +/- 1.5 g/dL (range 4-8 g/dL); the duration (+/- standard deviation) of disease was 2.1 +/- 1.1 years (range 1.5-8.5 years). None of the patients had growth retardation, malnutrition, or immunodeficiency. Abdominal symptoms included abdominal pain, diarrhea, and hematochezia in 1 patient. Nine other patients had no abdominal symptoms. Colonoscopy revealed actively motile T. trichiura worms in large numbers in the right colon in 7 patients, in the ileum in 1, in the left colon in 1, and worms carpeting of the whole colonic mucosa in 1. Associated mucosal changes included petechial lesions, blotchy mucosal hemorrhages, and active mucosal oozing. Biopsy of the colon revealed worm segments with a thick outer cuticle. The posterior segment of the worm contained gravid uterus with numerous characteristic T. trichiura eggs. There was paucity of associated mucosal changes in most of the sections. LIMITATIONS Similar studies in other endemic areas are lacking. CONCLUSION TDS should be considered in all patients in endemic areas with chronic iron deficiency anemia and/or occult blood loss.

Treatment of type I gastric neuroendocrine tumors with somatostatin analogs

Background and Aim:  There are limited data on response and long‐term follow‐up of octreotide therapy in type‐I gastric neuroendocrine tumors. The objective of the present study was to assess the response of type‐I gastric neuroendocrine tumors to octreotide‐long acting, repeatable (LAR) therapy and evaluate long‐term follow up of such patients after therapy.

Hepatobiliary and pancreatic ascariasis

Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.

Gastric Ascariasis Presenting as Unique Dyspeptic Symptoms in an Endemic Area

present in the fundus of the stomach and worms were seen entering the cardiac orifi ce and esophagus. We believe the symptoms were caused by movement of the worms into the esophagus in search of food, especially at night. Th ree patients had repeated episodes of cough and choking during night. EGD showed worms in the esophagus and fundus in one patient ( Figure 2 ) and in the fundus of the stomach in two patients. Th e remaining three patients had associated diseases as detected on EGD (cirrhosis with esophageal varices and hypertensive gastropathy-1, gastric carcinoma-1, and nodular lymphoid hyperplasia-1). Mucosa of the stomach in fi ve patients and the duodenal bulb in four patients showed multiple hemorrhagic erosions. Th ese were localized lesions presumably caused by injury at the site at which the mouth of the ascaride was biting or holding the mucosa. None of the patients presented with gastrointestinal bleeding. All patients reported to have vomited worms during the illness. Gastric ultrasound showed actively motile ascarides in the stomach. Ascarides were recognized by their characteristic long echogenic strips

Anomalous Pancreaticobiliary Ductal Union in Tropical Calcific Pancreatitis

CONTEXT Tropical calcific pancreatitis is unique to developing countries with of unknown origin. OBJECTIVE We evaluated the pattern of pancreaticobiliary ductal union in patients with tropical calcific pancreatitis. PATIENTS Twenty-one patients with tropical calcific pancreatitis were compared to 174 control subjects with no pancreaticobiliary disease and 35 patients with alcohol-induced chronic pancreatitis. MAIN OUTCOME MEASURE Two experienced people, blinded to the results, evaluated the pattern of pancreaticobiliary ductal union. Pancreaticobiliary ductal unions were classified as: separate ducts (no union), a short common-channel (length less than 6 mm), a long common-channel (length ranging 6-15 mm) and anomalous pancreaticobiliary ductal union (length greater than 15 mm). Anomalous union was defined as P-B type when the pancreatic duct appeared to join the bile duct and B-P type when the bile duct appeared to join the pancreatic duct. Any disparities between the two investigators were sorted out by mutual discussion. RESULTS Pancreaticobiliary ductal union in tropical calcific pancreatitis patients as compared to those in the control group was as follows: separate ducts, 23.8% vs. 49.4% (P=0.036); a short common-channel, 4.8% vs. 28.7% (P=0.017); a long common channel, 33.3% vs. 18.4% (P=0.144) and anomalous pancreaticobiliary ductal union, 38.1% vs. 3.4% (P<0.001). The B-P pattern of anomalous pancreaticobiliary ductal union was more frequent in tropical calcific pancreatitis than in the control group but there was no statistical significance (P=0.103). The angle of the pancreaticobiliary ductal union in the tropical calcific pancreatitis group was 88.1 + or - 36.2 degrees as compared to 20.0 + or - 11.5 degrees in control group (P<0.001). Alcohol-induced chronic pancreatitis (No. 35) predominantly had either separate ducts (65.7%) or a short common channel (25.7%). CONCLUSION We concluded that patients with tropical calcific pancreatitis in Kashmir had anomalous pancreaticobiliary ductal union, predominantly of B-P type with a wide angle of ductal union more frequently. This may be related to the etiology of tropical calcific pancreatitis in such regions.