Gamal Shiha

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4

BACKGROUND & AIMSnEgypt has the highest prevalence of chronic hepatitis C virus (HCV) infection in the world, and more than 90% of patients are infected with genotype 4 virus. We evaluated the efficacy and safety of the HCV polymerase inhibitor sofosbuvir in combination with ribavirin in HCV genotype 4 patients in Egypt.nnnMETHODSnTreatment-naïve or treatment-experienced patients with genotype 4 HCV infection (n=103) were randomly assigned to receive either 12 or 24 weeks of sofosbuvir 400 mg and ribavirin 1000-1200 mg daily. Randomization was stratified by prior treatment experience and by presence or absence of cirrhosis. The primary endpoint was the percentage of patients with HCV RNA <25 IU/ml 12 weeks after therapy (SVR12).nnnRESULTSnAmong all patients, 52% had received prior HCV treatment and 17% had cirrhosis at baseline. SVR12 rates were 90% (46/51) with 24 weeks and 77% (40/52) with 12 weeks of sofosbuvir and ribavirin therapy. Patients with cirrhosis at baseline had lower rates of SVR12 (63% 12 weeks, 78% 24 weeks) than those without cirrhosis (80% 12 weeks, 93% 24 weeks). The most common adverse events were fatigue, headache, insomnia, and anemia. Two patients experienced serious adverse events (cerebral ischemia, dyspnea). No adverse events resulted in treatment discontinuation.nnnCONCLUSIONnSofosbuvir plus ribavirin for 12 or 24 weeks is effective in treating both treatment-naïve and treatment-experienced Egyptian patients with genotype 4 HCV.

Gastric variceal ligation: a new technique

BACKGROUNDnGastric variceal bleeding is a serious complication of portal hypertension. The role of endoscopy in its management is still controversial. However, band ligation of gastric varices has not been evaluated. This study prospectively describes gastric variceal ligation as a new endoscopic technique for the management of different types of gastric varices.nnnMETHODSnGastric variceal ligation was performed in 27 patients with gastric varices: 3 patients had type 1 gastroesophageal varices, 14 had type 2, 8 had isolated gastric varices, and 2 had both type 1 and type 2 gastroesophageal varices. The etiology of portal hypertension was schistosomiasis in 9, post hepatic cirrhosis in 3, and mixed cirrhosis in 15 patients. The Child-Pugh classification was grade A in 6, B in 17, and C in 4 cases. Active variceal bleeding was present in 18 patients, whereas nonbleeding varices were encountered in 9 patients.nnnRESULTSnEmergency gastric variceal ligation arrested bleeding in 16 of 18 patients (88.8%). Recurrent bleeding was noted in 5 of 27 (18.5%). Six patients died (22.2%), 3 due to recurrent bleeding and 2 to liver failure. Variceal obliteration was achieved in all patients who underwent repeated elective sessions. The number of sessions needed for obliteration of varices was significantly less in patients with isolated gastric varices when compared with those with type 1 gastroesophageal varices ( p < 0.04). No serious complications occurred.nnnCONCLUSIONnGastric variceal ligation is a safe and effective treatment for the different types of gastric varices but especially isolated gastric varices.

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL).

Liver fibrosis is a common pathway leading to cirrhosis, which is the final result of injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Liver biopsy has been considered to be the “gold standard” to assess fibrosis. However, liver biopsy being invasive and, in many instances, not favored by patients or physicians, alternative approaches to assess liver fibrosis have assumed great importance. Moreover, therapies aimed at reversing the liver fibrosis have also been tried lately with variable results. Till now, there has been no consensus on various clinical, pathological, and radiological aspects of liver fibrosis. The Asian Pacific Association for the Study of the Liver set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The process for the development of these consensus guidelines involved the following: review of all available published literature by a core group of experts; proposal of consensus statements by the experts; discussion of the contentious issues; and unanimous approval of the consensus statements after discussion. The Oxford System of evidence-based approach was adopted for developing the consensus statements using the level of evidence from 1 (highest) to 5 (lowest) and grade of recommendation from A (strongest) to D (weakest). The consensus statements are presented in this review.

Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl(4)) rat model. Male Wistar rats received intraperitoneal injections of CCl(4) twice weekly for 8weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20mg/kg), nilotinib (10 and 20mg/kg) and silymarin (100mg/kg) during the last 4weeks of CCl(4)-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20mg/kg) was the most effective treatment to counteract CCl(4)-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10mg/kg), nilotinib (20mg/kg) and silymarin (100mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl(4)-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl(4)-induced fibrosis was ameliorated significantly by nilotinib (20mg/kg) and imatinib (20mg/kg). Unlike nilotinib, imatinib (20mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans.

Diagnosis and management of acute variceal bleeding: Asian Pacific Association for Study of the Liver recommendations

BackgroundAcute variceal bleeding (AVB) is a medical emergency and associated with a mortality of 20% at 6xa0weeks. Significant advances have occurred in the recent past and hence there is a need to update the existing consensus guidelines. There is also a need to include the literature from the Eastern and Asian countries where majority of patients with portal hypertension (PHT) live.MethodsThe expert working party, predominantly from the Asia–Pacific region, reviewed the existing literature and deliberated to develop consensus guidelines. The working party adopted the Oxford system for developing an evidence-based approach. Only those statements that were unanimously approved by the experts were accepted.ResultsAVB is defined as a bleed in a known or suspected case of PHT, with the presence of hematemesis within 24xa0h of presentation, and/or ongoing melena, with last melanic stool within last 24xa0h. The time frame for the AVB episode is 48xa0h. AVB is further classified as active or inactive at the time of endoscopy. Combination therapy with vasoactive drugs (<30xa0min of hospitalization) and endoscopic variceal ligation (door to scope time <6xa0h) is accepted as first-line therapy. Rebleeding (48xa0h of T0) is further sub-classified as very early rebleeding (48 to 120xa0h from T0), early rebleeding (6 to 42xa0days from T0) and late rebleeding (after 42xa0days from T0) to maintain uniformity in clinical trials. Emphasis should be to evaluate the role of adjusted blood requirement index (ABRI), assessment of associated comorbid conditions and poor predictors of non-response to combination therapy, and proposed APASL (Asian Pacific Association for Study of the Liver) Severity Score in assessing these patients. Role of hepatic venous pressure gradient in AVB is considered useful. Antibiotic (cephalosporins) prophylaxis is recommended and search for acute ischemic hepatic injury should be done. New guidelines have been developed for management of variceal bleed in patients with non-cirrhotic PHT and variceal bleed in pediatric patients.ConclusionManagement of acute variceal bleeding in Asia–Pacific region needs special attention for uniformity of treatment and future clinical trials.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high‐risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

The current and future disease burden of chronic hepatitis C virus infection in Egypt

2014 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update

Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the gold standard of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.