The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease.

BACKGROUND: Prostaglandins are cytoprotective agents that have been shown to benefit patients with a variety of acute and chronic liver diseases. Few data exist on the frequency of adverse effects of prostaglandins in these patients. METHODS: We retrospectively studied 105 patients with liver disease who were treated with either intravenous (i.v.) or oral prostaglandin E (PGE). Forty-four patients with primary nonfunction after liver transplantation and 36 patients with fulminant hepatic failure received i.v. PGE1 for 4.5 +/- 2.6 and 12.6 +/- 10.9 days, respectively. Twenty-five patients with recurrent hepatitis B viral infection after liver transplantation received oral PGE1 for 105 +/- 94 days or PGE2 for 464 +/- 399 days. RESULTS: Twenty-six of 80 patients (33%) receiving i.v. PGE1 developed gastrointestinal and/or cardiovascular side effects and 8% developed arthritis. Twenty-three of 25 patients (92%) who received high-dose oral PGE1 or PGE2 incurred arthritis and/or gastrointestinal adverse effects. Twenty-five patients received prolonged PGE therapy (oral > 60 days; i.v. > 28 days). Of this group, 23 (92%) developed clubbing and cortical hyperostosis resembling hypertrophic osteoarthropathy. All adverse effects were dose related and resolved with reduction or cessation of therapy. CONCLUSION: PGE therapy resulted in a wide spectrum of multisystem adverse effects which were reversible with reduction or cessation of therapy. Although the administration of PGE was safe and generally well tolerated, close medical supervision is necessary to avoid serious side effects.

Hepatopulmonary syndrome associated with schistosomal liver disease.

A 55-year-old man with schistosomal liver disease presented with shortness of breath, orthodeoxia, platypnea, cyanosis, marked digital clubbing and liver failure. Extensive investigation revealed no other etiology for liver disease apart from schistosomiases. The diagnosis of hepatopulmonary syndrome was based on clinical grounds, as well as abnormal arterial blood gases and positive contrast echocardiography. The patient underwent orthotopic liver transplantation, which was initially successful, but then died of respiratory complications and multi-organ failure on day 42 post-transplantation. To the authors' knowledge this is the first report of hepatopulmonary syndrome associated with schistosomal liver disease.

Impact of new AABB guidelines on hepatitis B and C testing among Saudi blood donors.

This study aims to compare the advantages and disadvantages of implementing the new American Association of Blood Banks (AABB) guidelines for hepatitis B and C against its old criteria for screening blood donors. Between July 1995 and December 2002, 63,368 consecutive blood donors were screening for hepatitis B and C according to the new guidelines. Cost and prevalence were analysed and compared with those found using the old AABB guidelines prior to July 1995. The overall percentage rate of deferred donors showed a significantly decrease to 19.3% in 2002, compared to 58.4% before July 1995 (P < 0.001). The new prevalence of hepatitis B and C among Saudi blood donors was found to be 1.7% and 0.6%, respectively, compared to 4% and 1.4%, respectively, under the old AABB guidelines. This resulted in a significant increase in the number and yield of blood units, and a decrease in the prevalence of hepatitis B and C was observed among screened donors. Using the new AABB guidelines, the estimated direct cost of donor screening for hepatitis B and C decreased significantly from 42.8 dollars per donor to 29.2 dollars per donor (P<0.001).

Role of endoscopic retrograde cholangiopancreatography before and after laparoscopic cholecystectomy.

BACKGROUND: While the role of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) in the diagnosis and management of choledocholithiasis is well established, this study evaluates the usefulness of ERCP and EST in patients with symptomatic cholecystolithiasis and suspected choledocholithiasis before undergoing laparoscopic cholecystectomy (LC), and the role of ERCP-EST in the management of complications resulting from LC. MATERIALS AND METHODS: This paper reviews retrospectively our experience from 1992 to 1995. A total of 1221 LCs and 717 ERCPs were performed, out of which 257 ERCPs were performed on 225 patients who underwent LC (230 ERCPs before and 27 after). The age range was 10-85 years (mean 43.5). The study group comprised 148 females (66%) and 77 males (34%). RESULTS: The overall success rate for ERCP was 92% (96% for diagnostic and 88% for therapeutic). Choledocholithiasis was found at preoperative ERCP in 45% of cases. Prediction of choledocholithiasis was accurate in 46%, based on abnormal liver chemistry, and 70% when based on a combination of abnormal liver tests and dilated main bile duct (>7 mm) by ultrasound. In 40 cases of acute biliary pancreatitis, choledocholithiasis was found at ERCP in eight cases (20%). In the post-LC group, all eight cases with residual stones and seven of eight cases with bile leaks were successfully treated endoscopically. There were four cases with major duct injuries that required surgical management. The complications related to ERCP-EST included two cases of bleeding post-EST (one was controlled with injection therapy and the second one was managed surgically), and three cases of mild pancreatitis. CONCLUSION: ERCP and EST are effective and safe in the diagnosis and management of choledocholithiasis, and facilitate LC for symptomatic cholelithiasis. The procedures are also valuable in the diagnosis and management of most complications resulting from LC.

Knowledge and Attitude towards Organ Donation among Males in Riyadh, Saudi Arabia.

Organ transplant programs are increasing in Saudi Arabia with the major barrier to transplantation being a shortage of organs. The majority of Saudi Nationals are reluctant and unwilling to donate or consent for donation. This study was undertaken to determine the knowledge and attitude towards organ donation among males in Riyadh, Saudi Arabia. A questionnaire was distributed to 223 men attending the out-patient department of the National Guard Hospital, Riyadh. A total of 205 (92%) individuals answered the questionnaire. Of them, 187 (91%) were Saudis and 18 (9%) were non-Saudis. A total of 187 (88%) had heard about organ donation of whom 80 (43%) each, had acquired this knowledge through television or radio, 16 (8%) through newspaper and magazines, seven (4%) through friends and relatives, and four (2%) through health-care workers. Of the 205 study subjects, 88 (43%) claimed they understood the concept of brain-death, 96 (47%) did not, and 19 (10%) did not respond to this question. One hundred and thirty-eight (67%) were willing to donate, and 156 (76%) were willing to receive an organ. One hundred and fifteen (56%) believed that Islam permits people to donate organs, five (2%) thought Islam does not permit organ donation, 64 (31%) gave a "don't know" answer and 21 (11%) did not attempt to answer the question. In addition, 41 (20%) thought organ donation disfigures the body. In conclusion although 67% of the respondents in this survey were willing to donate, there was a significant lack of knowledge and misconception with regard to Islamic support to, and the mutilating effects of, organ donation. Public educational programs and other measures addressing these issues may help in increasing the rate of organ donation among Saudis.

Cholestatic liver disease with ductopenia (vanishing bile duct syndrome) after administration of clindamycin and trimethoprim-sulfamethoxazole.

Two patients who developed cholestatic liver disease after exposure to antibiotics are described. One patient who received clindamycin had liver biopsy findings of marked cholestasis, portal inflammation, bile duct injury and bile duct paucity (ductopenia). A second biopsy after clinical improvement showed resolution of cholestasis but persistence of duct paucity. Three years later, treatment with ampicillin caused another episode of cholestatic hepatitis with cholestasis and duct paucity on rebiopsy. The second patient, who developed cholestasis after receiving trimethoprim-sulfamethoxazole, had marked duct paucity in the liver biopsy. This is the first description, to our knowledge, of ductopenia apparently caused by clindamycin. Cross-reactivity between clindamycin and ampicillin is also demonstrated in one patient. This report documents that duct paucity may occur within 10 days of onset of jaundice and appears to be confined to ducts less than 0.03 mm in diameter.

Primary sclerosing cholangitis in Arab children: report of four cases and literature review.

BACKGROUND: The prevalence of primary sclerosing cholangitis, a rare progressive liver disorder, is increasing with the advent of endoscopic retrograde cholangiography in the investigation of children with obscure liver disease. The etiology of primary sclerosing cholangitis is not known, clinical presentation is variable, treatment is only of limited success and long-term studies on prognosis in children are incomplete. Primary sclerosing cholangitis has not been described in Arab children. METHODS: To describe detailed clinical, laboratory, histologic and radiological features in 4 children with primary sclerosing cholangitis identified over a 2-year period at a tertiary referral center in Riyadh Saudi Arabia. RESULTS: Four children, all females, between the ages of 4 and 11 years with primary sclerosing cholangitis are identified. The diagnosis was suggested by the histology and confirmed by the characteristic cholangiographic findings. Clinical findings were itching in all 4 children, hepatomegaly in 3 and splenomegaly in 4 patients. Three of 4 patients had portal hypertension and 2 of these three variceal hemorrhage. Antinuclear and smooth muscle antibodies were negative in all four patients. None had clinical manifestations of chronic inflammatory bowel disease but microscopic colitis was documented in all 4 patients. CONCLUSIONS: Primary sclerosing cholangitis is present in Arab children with a prevalence rate of 5% in our study population.

Qualitative hepatic venous Doppler sonography versus portal flowmetry in predicting the severity of esophageal varices in hepatitis C cirrhosis.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of simple recognition of hepatic vein waveform abnormalities using Doppler sonography with portal Doppler flowmetry for the noninvasive assessment of esophageal varices in patients with hepatitis C cirrhosis. SUBJECTS AND METHODS: Fifty patients with biopsy-proven liver cirrhosis caused by hepatitis C who were being examined for possible liver transplantation were studied prospectively with Doppler sonography by a single observer. Hepatic vein waveforms were classified as normal triphasic, abnormal biphasic, monophasic, and those with loss of the reverse-flow component. Portal flow indicators included the maximum values of portal flow velocity, portal vein flow volume, diameter of the portal vein, and congestion index. For the purposes of this study, we simplified the endoscopic grading of varices by classifying F1 and F2 varices as small and F3 as large. None of the patients had clinical or echocardiographic signs of failure of the right side of the heart. RESULTS: Sensitivity for the detection of large varices was 92% for monophasic waves, 76% for waves with loss of the reverse flow component, and 62% for biphasic waves. Overall specificity was 100%. Portal vein diameter and congestion index were higher (p < .02) and portal vein velocity was lower (p < .05) in patients with varices than in patients without varices, but these indicators were not useful in determining the size of varices. Portal vein flow volume did not differ in the presence of varices or ascites and was independent of the morphology of the hepatic vein wave. CONCLUSION: Simple recognition of patterns seen in hepatic vein waveform morphology in patients with liver cirrhosis caused by hepatitis C is superior to portal Doppler flowmetry for predicting the size of esophageal varices.

Pharmacokinetics of a new oral formulation of cyclosporine in liver transplant recipients.

Trough concentrations of cyclosporine can be highly variable because of its poor bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a new microemulsion of cyclosporine is more readily absorbed than SIM in healthy controls. The present study compared the pharmacokinetic profiles of SIM and N-SIM following orthotopic liver transplantation. In 16 patients with partial biliary diversion, 1 week after transplantation, the bioavailability and peak concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p = 0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p = 0.004) conditions. Trough concentrations were similar for the two formulations. However, peak concentrations were higher for N-SIM in both fasting (+119%, p = 0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N-SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The correlation between trough concentrations and bioavailability was greater for N-SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that the rate of absorption and the bioavailability of N-SIM is significantly and consistently better than SIM and may, therefore, improve the therapeutic index of cyclosporine after liver transplantation.

Liver transplantation at king fahad national guard hospital riyadh, kingdom of saudi arabia.

Liver disease is a major medical problem in the Kingdom of Saudi Arabia and is mostly due to viral hepatitis. Liver transplantation is the only option for patients with end-stage liver disease offering good long-term survival. The first liver transplant at the King Fahad National Guard Hospital was performed in February 1994 and since then, 40 liver transplants have been performed on 37 patients. Immunosuppression consisted of prednisone combined with cyclosporin (Neoral) or FK 506. Maintenance immunosuppression was with the use of cyclosporin or FK 506 as monotherapy. All, but one patient, survived the surgical procedure; there were no cases of primary non-function; acute cellular rejection occurred in 12 patients all of whom responded to steroids. Pneumonia and biliary sepsis occurred in 12 patients each. A total of 10 patients died, with sepsis being the leading cause of death. The overall graft survival was 73%. Donor shortage continues to be a major limiting factor.