Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: A comparative analysis.

In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct-acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early-phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV-infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA-exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow-up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02-7.25), which was similar in the multivariable-adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.

National treatment programme of hepatitis C in Egypt: Hepatitis C virus model of care.

Hepatitis C virus (HCV) infection is a major health problem in Egypt as the nation bears the highest prevalence rate worldwide. This necessitated establishing a novel model of care (MOC) to contain the epidemic, deliver patient care and ensure global treatment access. In this review, we describe the process of development of the Egyptian model and future strategies for sustainability. Although the magnitude of the HCV problem was known for many years, the HCV MOC only came into being in 2006 with the establishment of the National Committee for Control of Viral Hepatitis (NCCVH) to set up and implement a national control strategy for the disease and other causes of viral hepatitis. The strategy outlines best practices for patient care delivery by applying a set of service principles through identified clinical streams and patient flow continuums. The Egyptian national viral hepatitis treatment programme is considered one of the most successful and effective public health programmes. To date, more than one million patients were evaluated and more than 850 000 received treatment under the umbrella of the programme since 2006. The NCCVH has been successful in establishing a strong infrastructure for controlling viral hepatitis in Egypt. It established a nationwide network of digitally connected viral hepatitis-specialized treatment centres covering the country map to enhance treatment access. Practice guidelines suiting local circumstances were issued and regularly updated and are applied in all affiliated centres. This review illustrates the model and the successful Egyptian experience. It sets an exemplar for states, organizations and policy-makers setting up programmes for care and management of people with hepatitis C.

Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt.

In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan(©)), and serum markers (APRI, Fib4 and Fibrotest(©)). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.

The future for the treatment of genotype 4 chronic hepatitis C.

Hepatitis C virus genotype 4 (HCV-4) is the most common type of hepatitis C virus (HCV) in the Middle East and Africa, in particular Egypt. Since the development of new protease inhibitors, the response of HCV-4 to the standard regimen of treatment (pegylated interferon/ribavirin) lags behind other genotypes and has become the most resistant type to treat. The development of therapeutic strategies for all patients with HCV-4 whether they are naïve, have experienced a virological breakthrough, are relapsers or non-responders is still a considerable challenge. New types of interferon (Consensus Interferon, Y-shaped, Albinterferon...) and new direct action antiviral drugs (Nitazoxanide, Vit.D, other) may improve the treatment of patients with HCV-4. The IL28B CC polymorphism may be associated with sustained virological response.

Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt.

BACKGROUND: Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1-3. The national program in Egypt is using SOF-DCV combination for large scale treatment. AIM: To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting. METHODS: Data and outcome of chronic HCV patients who were treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the national hepatitis C treatment program in Egypt are presented. Treatment-naïve patients without cirrhosis were treated without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored. RESULTS: During the first 2 months of the programme, 18 378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV. Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7% for patients treated with RBV, P = .32). Treatment was prematurely discontinued in only 1.5% of patients. The most common events leading to discontinuation were patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within this group. CONCLUSIONS: Real-world experience of generic SOF-DCV in patients with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.

Gastric mucosa-associated lymphoid tissue lymphoma associated with pancreatic non-Hodgkin's lymphoma: A case report.

UNLABELLED: Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal lymphomas that arise from B lymphocytes located in the marginal zone of lymphoid follicles. Although, there is a substantial amount of lymphoid tissue in the gastrointestinal tract, MALT lymphomas usually arise in chronically inflamed sites that are normally devoid of lymphoid tissue. The best example is gastric MALT lymphoma that is almost always associated with Helicobacter pylori. Primary pancreatic lymphoma (PPL) is an extremely rare tumor (1% incidence) and is often confused with pancreatic adenocarcinoma. By suspecting PPL on clinical and imaging grounds, surgery and its associated complications can be avoided, since the mainstay of the treatment is non-surgical strategies including chemotherapy. We represent a case of a 45-year-old male presented with abdominal pain and vomiting. Upper endoscopy showed multiple gastric ulcers, biopsies revealed non-specific inflammatory ulcers. The patient was given 4-weeks course of proton pump inhibitor with no improvement. After few months, he complained of severe abdominal pain relieved by leaning forward and associated with repeated vomiting. Upper endoscopy revealed multiple umbilicated gastric masses, 10-20 mm in diameter. Biopsies were taken, histopathology and immunohistochemistry revealed MALT lymphoma. Endoscopic ultrasonography was done to the patient and it showed a pancreatic head mass, fine-needle aspiration was done, histopathology and immunohistochemistry revealed PPL. The patient received chemotherapy for MALT lymphoma with near total relief of symptoms and disappearance of gastric and pancreatic masses. CONCLUSION: This is a rare case having MALT lymphoma associated with PPL.

Improvement of steatosis after interferon therapy in HCV genotype 4 is related to weight loss.

INTRODUCTION: Hepatic steatosis is common in patients with chronic hepatitis C virus (HCV) infection, and its occurrence may be related to both host and viral factors. Relationship between improvement in steatosis and response to anti-viral treatment remains unclear. This study assessed the factors associated with steatosis in patients infected with genotype 4 HCV, and to correlate degree of changes in steatosis with host factors and response to treatment. METHODS: Records of 175 patients with chronic genotype 4 HCV infection, who had received interferon and ribavirin combination therapy, were reviewed retrospectively to extract data on body mass index (BMI), presence of diabetes mellitus, and liver histology findings. Paired BMI data and liver biopsies (pre- and 24-weeks post-treatment) were available in 86 patients. Baseline steatosis and its changes (before and after treatment) were the dependent variables in a univariate and multivariate analyses. RESULTS: Steatosis was found in 88/175 (50.3%) of baseline biopsies. Its presence was related to baseline BMI (r=0.33, P<0.01), but not with viral load, or grade of liver inflammation or fibrosis. On follow up, improvement in steatosis was significantly associated with degree of weight loss but not with response to anti-viral treatment. CONCLUSION: Steatosis is common in genotype 4 HCV infection, and its presence appears to be related to high BMI, but not to viral load or degree of liver injury.