My 40-Year Encounter with ERCP: A Saga of Service, Syndromes, and Solutions.

Endoscopic retrograde cholangiopancreatography (ERCP) has been a significant development in gastrointestinal endoscopy. I did my first ERCP at SKIMS on December 5, 1982, and over the last 40 years, I have performed 10,100 ERCP procedures, including 600 Sphincter of Oddi manometries (SOM), and 3200 therapeutic ERCPs. We were confronted with many clinical challenges that needed answers by applying ERCP as a primary diagnostic tool. These studies gave birth to and/or recognition of several clinical syndromes. The hepatobiliary and pancreatic ascariasis (HBPA) as a clinical disease was recognized in 1985. The nematode, Ascaris lumbricoides, was the most common cause of hepatobiliary and pancreatic diseases in Kashmir, and its impact on healthcare, clinical profile, management policies, and control measures was identified. Kashmir was recognized as an endemic zone for recurrent pyogenic cholangitis (RPC), which constituted 12.5% of all biliary diseases. RPC in this population was found essentially to be an aftermath of HBPA. A subset of patients with hepatic hydatidosis with rupture into the biliary tract was recognized at ERCP and primarily treated by endotherapy. Cholangiographic abnormalities in children with portal cavernoma evolved into the recognition of portal biliopathy. Extensive studies of the sphincter of Oddi manometry in patients with unexplained biliary and/or pancreatic pain following cholecystectomy identified the entity of the sphincter of Oddi dyskinesia (SOD). In a cross-over trial, Nifedipine, compared with a placebo, showed a significant clinical response in 20 of 28 such patients. ERCP studies done in patients with tropical calcific pancreatitis showed an anomalous union of bile and pancreatic ducts. Forty of the 220 patients with liver transplantation had biliary complications namely biliary leaks, bile duct strictures, SOD, and recurrence of underlying primary biliary cholangitis. Biliary complications caused considerable morbidity and mortality in patients with liver transplantation.

Percutaneous Drainage in Hepatic Hydatidosis-The PAIR Technique: Concept, Technique, and Results.

Over decades, surgery has been the only accepted mode of treatment for liver hydatid cysts. It had been a surgical dogma for a long that hydatid disease is an absolute contraindication for needle puncture/aspiration as it can cause anaphylaxis, death, and dissemination. We envisaged prospectively perform percutaneous drainage as a primary form of treatment for hepatic hydatidosis. Through extensive and very careful experimentation, we proved that aspiration of hydatid cysts can be performed safely and is the ideal way to manage a subset of patients with hydatid cysts in the liver. The patient and cyst characteristics good and not good for percutaneous drainage were carefully selected. The procedure of percutaneous drainage of hepatic hydatid cysts involves four sequential steps as defined in the alphabets of the title PAIR, denoting puncture (P), Aspiration (A), Instillation (I), and Reaspiration (R). During and postprocedure, we enforced strict monitoring given the anticipated anaphylaxis. The first PAIR procedure was performed in June 1988. The results of percutaneous drainage of 21 cysts in 12 patients were reported in 1991. Next, a prospective study was done to show that concomitant Albendazole therapy is recommended as an adjuvant to percutaneous drainage for hepatic hydatidosis. In a seminal prospective study comparing percutaneous drainage and surgery, we showed that percutaneous drainage is as good as surgery in the management of uncomplicated hydatid cysts with fewer complications and shorter hospital stays. Lastly, long-term follow-up results of percutaneous drainage on a large cohort of patients with hepatic hydatid cysts were reported, with excellent results and no evidence of local, peritoneal or systemic dissemination. Based on these data percutaneous drainage, the so-called PAIR technique has established itself as a novel therapeutic advance in hepatic hydatid disease.

COVID-19 Vaccines: A Race Against Time in the Middle of Death and Devastation!

The coronavirus disease 2019 (COVID-19) has turned into a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks, and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are "rate-limiting" and "time-consuming", many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human "challenge experiments" to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine, and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying "Quick fix" and "short cuts" can lead to errors with disastrous consequences.

The Discovery of Hepatitis Viruses: Agents and Disease.

Discovery of five hepatitis viruses A to E has followed distinctive definable phases. Human experiments at Willowbrook identified two forms of hepatitis namely infectious hepatitis and serum hepatitis. The discovery of Australia antigen in 1965 led to rapid scientific developments in viral hepatitis. SH antigen was detected in sera of patients with serum hepatitis and soon SH antigen and Australia antigen were found to be identical and selectively associated with serum hepatitis. In 1970, 42-nm Dane particles were detected in Australia antigen positive sera and linked to the virus of serum hepatitis. Subsequently, a new antigen-antibody system (e-antigen/antibody) was detected in such patients and associated with infectivity. Then, DNA polymerase was found in concentrated pellets containing Australia antigen. Hepatitis B virus (HBV) DNA cloning and sequencing of HBV followed these developments. In 1973, 27 nm hepatitis A virus (HAV)-like particles were visualized in stool samples obtained during acute phase of illness after inoculation of MS-1 strain in volunteers. Cloning and sequencing of HAV followed. In 1977, a new antigen-antibody system (δ antigen-antibody system) was identified by chance associated with HBV. Based on animal transmission studies, δ agent was found to be another virus called hepatitis D virus that is defective, requires the helper functions of HBV and interferes with HBV replication. The search for hepatitis C virus started when non-A, non-B hepatitis was recognised in multiply transfused patients with subsequent successful animal transmission. HCV was identified by a novel immunoscreening approach involving screening of cDNA libraries from infectious sera. The story of hepatitis E is historically linked to discovery of waterborne epidemic non-A, non-B hepatitis from Kashmir, India. Virus-like-particles of the agent were identified in stool samples of a human volunteer after a self-experimentation. HEV cDNA was detected in bile-enriched infectious samples and full-length HEV RNA genome was subsequently cloned and sequenced.

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.

Portal biliopathy.

Portal biliopathy refers to cholangiographic abnormalities which occur in patients with portal cavernoma. These changes occur as a result of pressure on bile ducts from bridging tortuous paracholedochal, epicholedochal and cholecystic veins. Bile duct ischemia may occur due prolonged venous pressure effect or result from insufficient blood supply. In addition, encasement of ducts may occur due fibrotic cavernoma. Majority of patients are asymptomatic. Portal biliopathy is a progressive disease and patients who have long standing disease and more severe bile duct abnormalities present with recurrent episodes of biliary pain, cholangitis and cholestasis. Serum chemistry, ultrasound with color Doppler imaging, magnetic resonance imaging with magnetic resonance cholangiopancreatography and magnetic resonance portovenography are modalities of choice for evaluation of portal biliopathy. Endoscopic retrograde cholangiography being an invasive procedure is indicated for endotherapy only. Management of portal biliopathy is done in a stepwise manner. First, endotherapy is done for dilation of biliary strictures, placement of biliary stents to facilitate drainage and removal of bile duct calculi. Next portal venous pressure is reduced by formation of surgical porto-systemic shunt or transjugular intrahepatic portosystemic shunt. This causes significant resolution of biliary changes. Patients who persist with biliary symptoms and bile duct changes may benefit from surgical biliary drainage procedures (hepaticojejunostomy or choledechoduodenostomy).

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.

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.

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.

Accuracy of Rapid Point-of-Care Diagnostic Tests for Hepatitis B Surface Antigen-A Systematic Review and Meta-analysis.

BACKGROUND: Rapid point-of-care tests provide plausible diagnostic strategy for hepatitis B surface antigen (HBsAg) in low resource areas. However, their utility depends upon their overall performance. Our objective was to meta-analyze the diagnostic accuracy of rapid point-of-care tests for HBsAg. METHODS: Literature search was done with the help of a metasearch engine Metta, a query interface for retrieving articles from five leading medical databases. Studies that employed rapid point-of-care tests for detection of HBsAg and compared the results with reference test were included. Two reviewers performed quality assessment of the studies and extracted data for estimating test accuracy. Twenty-seven studies were meta-analyzed and stratified by multiple parameters. RESULTS: Twenty-seven studies had evaluated 49 test brands and generated 76 data points. Sensitivity of individual tests varied widely and were heterogeneous (range 43.5%-99.8%); while specificity estimates were more robust and close to 100% (range 90%-100%). Overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio for all tests were 97.1% (95% CI, 96.1%-97.9%), 99.9% (CI, 99.8%-100%), 118.4 (CI, 84.7-165.5), 0.032 (CI, 0.023-0.045) and 4094.7 (CI, 2504.1-6600.8) respectively. This suggested high pooled accuracy for all studies. We found substantial heterogeneity between studies. Three factors (study location, reference standard and study score) appeared most strongly associated with test estimates and observed heterogeneity. The Determine test showed consistency in performance in studies done across developed and developing countries and the Determine and the BinaxNOW tests had significantly higher estimates than pooled estimates of remaining tests. Tests revealed analytical sensitivity of 4 IU/ml against manufacturer's claim of 0.5 IU/ml; reduced sensitivity with HBsAg mutants and poor performance in seroconversion panels. CONCLUSIONS: Tests with better analytical sensitivity need to be developed and their feasibility and outcomes in various clinical settings need to be addressed.

Diffuse duodenal nodular lymphoid hyperplasia: a large cohort of patients etiologically related to Helicobacter pylori infection.

BACKGROUND: Nodular lymphoid hyperplasia of gastrointestinal tract is a rare disorder, often associated with immunodeficiency syndromes. There are no published reports of its association with Helicobacter pylori infection. METHODS: From March 2005 till February 2010, we prospectively followed all patients with diffuse duodenal nodular lymphoid hyperplasia (DDNLH). Patients underwent esophagogastroduodenoscopy with targeted biopsies, colonoscopy, and small bowel video capsule endoscopy. Duodenal nodular lesions were graded from 0 to 4 based on their size and density. Patients were screened for celiac sprue (IgA endomysial antibody), immunoglobulin abnormalities (immunoglobulin levels & serum protein electrophoresis), small intestine bacterial overgrowth (lactulose hydrogen breath test), and Helicobacter pylori infection (rapid urease test, and histological examination of gastric biopsies). Patients infected with Helicobacter pylori received sequential antibiotic therapy and eradication of infection was evaluated by 14C urea breath test. Follow up duodenoscopies with biopsies were performed to ascertain resolution of nodular lesions. RESULTS: Forty patients (Males 23, females 17; mean age ± 1SD 35.6 ± 14.6 years) with DDNLH were studied. Patients presented with epigastric pain, vomiting, and weight loss. Esophagogastroduodenoscopy showed diffuse nodular lesions (size varying from 2 to 5 mm or more) of varying grades (mean score ± 1SD 2.70 ± 0.84) involving postbulbar duodenum. Video capsule endoscopies revealed nodular disease exclusively limited to duodenum. None of the patients had immunoglobulin deficiency or small intestine bacterial overgrowth or positive IgA endomysial antibodies. All patients were infected with Helicobacter pylori infection. Sequential antibiotic therapy eradicated Helicobacter pylori infection in 26 patients. Follow up duodenoscopies in these patients showed significant reduction of duodenal nodular lesions score (2.69 ± 0.79 to 1.50 ± 1.10; p < 0.001). Nodular lesions showed complete resolution in 5 patients and significant resolution in remaining 21 patients. Patients with resistant Helicobacter pylori infection showed no significant reduction of nodular lesions score (2.71 ± 0.96 to 2.64 ± 1.15; p = 0.58). Nodules partially regressed in score in 2 patients, showed no interval change in 10 patients and progressed in 2 patients. CONCLUSIONS: We report on a large cohort of patients with DDNLH, etiologically related to Helicobacter pylori infection.

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.

Preduodenal portal vein with preduodenal common bile duct: an extremely rare anomaly.

Preduodenal portal vein (PDPV) may occur as an isolated event and result in no symptoms, or it may found at autopsy as an incidental finding; associated preduodenal common bile duct (PDCBD) is an extremely rare event. To the 8 reported cases of PDPV with PDCBD, we add this rare case. Such a discovery is often incidental and of little import; however, it takes on major importance for hepatobiliary surgeons because the accidental damage of PDPV with PDCBD can lead to serious consequences. In addition to describing and illustrating this case, we discuss its relevant anatomy, embryology and associated malformations.

Hepatitis E virus.

PURPOSE OF REVIEW: Hepatitis E is an emerging infectious disease. This review will focus on recent advances in the zoonotic transmission, global distribution and control of hepatitis E. RECENT FINDINGS: Hepatitis E virus infection is known to cause waterborne epidemics and sporadic infections in developing countries. Recently, there have been several reports on zoonotic foodborne autochthonous infections of hepatitis E in developed countries. Hepatitis E typically causes self-limited acute infection. Recent reports have documented hepatitis E virus causing chronic hepatitis and cirrhosis in patients after solid organ transplantation. High incidence and severity of hepatitis E in pregnant women have been re-confirmed. The reason for high mortality in pregnant women remains ill understood. A recombinant hepatitis E vaccine has been evaluated in a phase 2, randomized, placebo-controlled trial in Nepal and was found to be well tolerated and efficacious. SUMMARY: There has been considerable advance in understanding the epidemiology of hepatitis E virus infections in western countries. The occurrence of chronic hepatitis in organ transplant recipients opens a new chapter in hepatitis E epidemiology. The report on an efficacious and well tolerated recombinant vaccine gives hope for control of the disease in the near future.

Biliary disease after liver transplantation: the experience of the King Faisal Specialist Hospital and Research Center, Riyadh.

BACKGROUND AND AIM: The biliary tract has been referred to as the "Achilles heel" of liver transplantation. The aim of this study was to document the frequency, clinical presentation and management of biliary complications after liver transplantation in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia. METHODS: The liver transplant clinic at KFSH&RC has registered and followed 220 patients (150 male and 70 female patients; age 40.6 +/- 18.6 years; pediatric 33, adult 187) during the period from 1987 to June 2003. A total of 235 transplants were carried out on these patients. Cadaveric liver transplants had been carried out on 202 patients, non-heart beating liver transplant in three patients, live donor liver transplants in 11 and split transplant in four. Biliary reconstruction was duct-to-duct anastomosis in 147 patients and Roux-en-Y in 73. Biliary complications were suspected on clinical and biochemical parameters and confirmed using imaging techniques. RESULTS: Forty patients (18.2%) developed 53 biliary complications. These included bile leak in 16, strictures in 25, calculi in eight, and sphincter of Oddi dysfunction and possible recurrence of primary sclerosing cholangitis in the donor duct in two patients each. Bile leaks were observed in the early postoperative period (median period 30 days, range 1-150 days, 95% confidence interval [CI] 8-51). Leakage occurred at the anastomotic site in 13 patients. Patients presented with bilious drainage (n = 6), abdominal pain at T-tube removal (n = 3), fever (n = 2), sepsis (n = 1), dyspnea (n = 1) and abnormal liver tests (n = 3). Eleven patients had intra-abdominal bilious collections. Two patients were treated conservatively, eight patients had ultrasound-guided aspiration of biloma, five had biliary stenting at endoscopic retrograde cholangiopancreatography and two patients needed surgery. There were four deaths, two of which were related to bile leak, one patient was left with permanent external biliary drainage and four patients had biliary strictures in the follow-up period. Biliary strictures occurred at a median period of 360 days (range 4-2900 days; 95% CI 50-670) after the transplant. Hepatic artery thrombosis caused biliary strictures in three, while 21 strictures were localized to the anastomotic site. Biliary strictures presented with elevated liver tests in five patients, progressive cholestasis in five, cholangitis (with septicemia in five) in 11, abdominal pain in two and acute pancreatitis in three patients. Repeat sessions of endoscopic or percutaneous dilatation and stenting (mean sessions 4.4/patient, range 3-7) were attempted in 20 patients to relieve strictures, with success in only nine patients. Seven patients had surgery. Four patients with biliary strictures died. Biliary calculi developed late in the follow-up period and had the appearance of biliary casts in five and sludge in three patients. Eleven (27.5%) patients with biliary disease died compared with 35 (19.4%) patients without biliary disease. CONCLUSIONS: Biliary complications occurred in 18.2% of patients after liver transplantation and included biliary leak and biliary strictures with or without calculi. Management involved a combination of endoscopic, radiologic and operative procedures. Biliary complications caused considerable morbidity and mortality in liver transplant patients.

Meta-analysis: a randomized trial of peginterferon plus ribavirin for the initial treatment of chronic hepatitis C genotype 4.

BACKGROUND: Guidelines for treatment of patients infected with hepatitis C virus genotype 4 are not available. AIM: To perform a meta-analysis of randomized controlled trials comparing peginterferon plus ribavirin with interferon plus ribavirin treatment in treatment-naive patients infected with chronic hepatitis C virus genotype 4. METHODS: The outcome measure was sustained virologic response. The measure of association employed was relative risk calculated by the random-effect model, with heterogeneity, sensitivity and subgroup analyses. RESULTS: Of the 565 studies screened, six randomized controlled trials including 424 patients (peginterferon plus ribavirin 219, interferon plus ribavirin 205) were analysed. Duration of therapy was 1 year in all trials. Sustained virological response obtained with peginterferon plus ribavirin (55%) was significantly higher than with interferon plus ribavirin (30%) [relative risk, 1.71 (95% confidence interval, 1.15-2.56); P = 0.0088]. In the subgroup analyses, sustained virological response in trials using standard-dose ribavirin (1000 or 1200 mg/day) was 72% as against 45.8% in trials using low-dose ribavirin (800 mg/day) (P = 0.01). Further sub-group analyses for treatment duration, body weight, viral load and cirrhosis could not be performed because of lack of relevant data. CONCLUSION: Treatment-naive patients infected with hepatitis C virus genotype 4 should be treated with peginterferon plus standard-dose ribavirin for 1 year, with an expected sustained virological response rate of 72%.