Maha M Elsabaawy

Khat-induced liver injuries: A report of two cases.

Khat is consumed for recreational purposes in many countries, including Yemen, where >50% of adults chew khat leaves regularly. A wide spectrum of khat-induced liver injuries has been reported in the literature. Herein, we report two patients with khat-induced liver injury. Both patients clinically presented with acute hepatitis, one of whom showed radiological evidence of hepatic outflow obstruction. Based on the histological tests, both patients had acute hepatitis, which indicated drug-induced liver injury (DILI) on a background of chronic hepatitis and portal fibrosis; of the two, one presented with symptoms of immune-mediated liver injury.

The role of IL‐28, IFN‐γ, and TNF‐α in predicting response to pegylated interferon/ribavirin in chronic HCV patients

The primary goal of HCV therapy is to achieve a sustained virological response (SVR). Many host and viral factors influence the treatment response. Cytokines play an important role in the defense against viral infections, where successful treatment of hepatitis C depends on a complex balance between pro‐ and anti‐inflammatory responses. In the present study, we investigated the relationship between the presence and percentage of some cytokines (IL‐28, IFN‐γ, and TNF‐α) regarding different clinicopathological parameters including response to therapy in chronic HCV patients using immunohistochemical technique. This study was carried out on 64 chronic HCV patients (34 responders and 30 non‐responders). Of cases, 54% showed IL‐28 expression, which was associated with low AST (p = 0.002) and low HAI score (p = 0.006). Of cases, 67 and 45% showed IFN‐γ and TNF‐α expression, respectively, where the median percentage of TNF‐α expression was higher in grade II spotty necrosis compared to grade I. Some inflammatory cytokines expressed by intrahepatic inflammatory cells in chronic HCV patients promote inflammation and injury (pro‐inflammatory) such as TNF‐α. Other cytokines aid in resolving inflammation and injury (anti‐inflammatory) such as IL‐28. The balance between these cytokines will determine the degree of inflammatory state. None of the investigated cytokines proved its clear cut role in affecting response to therapy, however, their levels varied between responders and non‐responders for further investigations to clarify.

Hepatocellular carcinoma following direct anti-viral for hepatitis C treatment: a report of an Egyptian case series

Egypt had been vexed by the highest load of chronic hepatitis C in the world. It represents a vast market of the new direct-acting anti-viral drugs (DAAs); effectively treating chronic hepatitis C virus (HCV) infection. Eradication of HCV in Egypt has been challenged by the observed increased diagnosis of hepatocellular carcinoma (HCC) in relation to DAAs therapy. This is the first Egyptian report annotating to a series of sixteen chronic HCV infected cases without a diagnosis of HCC before DAAs therapy and unexpected development of HCC during or after completion of DAAs therapy.

The Role of Monocyte/Macrophage and CXCR3 in Differentiation between Recurrent Hepatitis C and Acute Cellular Rejection Postliver Transplantation

Objective Liver transplantation (LT) is the recommended treatment for patients with advanced liver disease and cirrhosis in all guidelines, mostly as a complication of HCV. The distinction between reinfection of the graft with HCV and acute cellular rejection (ACR) is essential because they are managed differently. Hepatic macrophages, which can either arise from circulating blood-derived monocytes (BDM) or from resident tissue Kupffer cells, are central in the pathogenesis of chronic liver injury. The aim of this work was to evaluate whether the origin of macrophages and the immune mediator CXCR3 could help in differentiating between acute recurrent HCV and ACR after liver transplantation. Methods Twenty-nine cases of recurrent hepatitis C and 26 cases of ACR were included in this study. The expression of CD 68 (macrophage marker), CD11b (BDM marker), and CxCR3 in the postliver transplant biopsy using immunohistochemistry was determined. Results CD11b expression highlighting macrophages of BDM origin was in favor of recurrent hepatitis C (P < 0.001) than in ACR (P = 0.44), while CXCR3 expression by hepatocytes was in favor of ACR (P = 0.001). Conclusion Macrophage infiltrating liver tissue post LT can distinguish between ACR by upregulation of CXCR3 and recurrent hepatitis C by predominant CD11b.

Inosine Triphosphate Pyrophosphatase Gene Polymorphisms and Ribavirin-Induced Anemia in HCV Patients

In spite of the interferon (INF) redundancy in treating HCV, ribavirin (RBV) is still included with the new direct antiviral therapies. Ribavirin-induced hematological alterations had been referred to ITPA gene polymorphisms. Objective: Evaluate ITPA gene polymorphisms (rs1127354 and rs7270101) with development of anemia in chronic hepatitis C (CHC) Egyptian patients during treatment with pegylated-interferon (Peg-IFN) plus ribavirin (RBV). Methods: 100 Egyptian CHC patients treated with PEG-IFN/RBV were recruited, 55 patients developed anemia (Hb decline>2 g/dl), and other 45 would not developed anemia (Hb decline ≤ 2 g/dl) at week 12 throughout the treatment course. Routine laboratory investigations were done for all participates (HCV-Abs, HBs Ag, HCV-RNA levels, complete blood picture, liver and kidney function tests. Single nucleotide polymorphism (SNP) was done by ABI TaqMan allelic discrimination kit for ITPA polymorphisms (rs1127354 and rs7270101). Results: CC and AA were the most prevalent genotypes of SNPs rs1127354 and rs7270101 respectively among two studied groups. rs1127354 polymorphism was associated with Hb-decline at week 12 of treatment and with rs7270101 polymorphism for predicting platelet decline during treatment. Lower levels of platelet decline were detected with CC rs1127354 and AA rs7270101. Conclusion: While ITPA polymorphisms rs1127354 CC genotype carried a predilection of anemia occurrence in PEG-IFN/RBV HCV treated subjects, the minor allele rs1127354 AA plays a crucial role in their protection. Platelet decline was reported in both ITPA rs1127354 and rs7270101 polymorphisms. Screening for ITPA polymorphisms in Egyptian HCV patients would be of value in avoiding hematological disturbances and dose modulations in RBVbased therapies.

IgG4 Sclerosing Cholangitis and Post Infantile Giant Cell Hepatitis: A Case Report of an Extraordinary Co-presentation

Background: Giant cell hepatitis is rarely described in adults; referred to as post infantile giant cell hepatitis (PIGCH). Most reports have mentioned PIGCHs association with systemic lupus erythromatosis, autoimmune hepatitis, lymphoma, and leukemia. However, links with other medical disorders are still evolving. Reports of primary sclerosing cholangitis (PSC) presenting as IgG4-SC has been typically described in association with other IgG4-related disorders, most frequently autoimmune pancreatitis. However, some cases of isolated IgG4-SC have been reported. Herein; we report a case of IgG4-SC presented by PIGCH. Case description: A 29-year-old gentleman presented with two month jaundice and biochemical evidence of acute hepatitis. He reported no history of drug exposure, had no gall bladder or pancreatic disease, nor prior similar attacks. The work up revealed negative serology for viral hepatitis. Markers of autoimmune liver disease were negative except for pANCA, and serum levels of pancreatic enzymes, copper and ceruplasmin were normal, and urinary copper was normal. Results: Abdominal sonography and MRCP showed normal pancreas and biliary tract. ERCP showed that the common bile duct had a single short narrowed segment with thickened walls. Histological examination of colonoscopic biopsies taken from the terminal ileum and colon demonstrated no pathological alterations. Liver histology showed evidence of parenchymal extinction with extensive giant cell transformation, ductular proliferation, cholestasis, and positive IgG4 staining, a picture suggestive of PSC and PIGCH. Discussion: In this case, we did not test for serum levels of IgG4, and resorted to immune-staining of liver tissue, as this is the hallmark for diagnosing IgG4-SC. Histopathological features and, more definitely, the positive IgG4 immunostaining were present in the liver tissue, which were crucial in diagnosing this case as IgG4-SC (IAC). Conclusion: This case presented with both IgG4-SC and biopsy proven PIGCH, and had a favourable outcome with biliary drainage and immuno-suppression therapy

Acute Hepatitis C Virus Infection and Directly Acting Anti-Hepatitis C Virus Drugs

The best of care of Acute hepatitis C (AHC) infections in the evolving era of all oral directly acting antiviral drugs (DDAs) needs revision. The inevitable chronic liver disease in 80% of AHC infections justifies the advent of DDAs that expectedly will guarantee high cure rates. Unlike interferons, the short and ultra-short all oral DDAs regimens had revolutionized treatment strategies with better adherence and fewer complications. However, the costly price of DAAs added to the average expertise is still contrarily active. Up-to-date, studies concerning DAAs treatment for AHC mono-infection are sparse; indeed this represents an unmet need in modern AHC management.

Sarcoidosis-Lymphoma Syndrome presenting by severe Cholestatic Hepatitis

Severe cholestatic hepatitis is an uncommon presentation of either sarcoidosis or Hodgkin lymphoma. Sarcoidosis lymphoma syndrome is a rare disorder with sarcoidosis heralding the onset of lymphoma. Here we report a case of coexisting sarcoidosis-Hodgkin’s lymphoma syndrome presenting with severe cholestatic hepatitis.

Hereditary Spherocytosis Evolving to Non-Hodgkin Lymphoma

Hereditary spherocytosis is rarely seen to occur simultaneously in association with lymphomas or hematological malignancies. Here in, we describe a case of hereditary spherocytosis associated with diffuse follicular Non-Hodgkin lymphoma.

Congenital Hepatic Fibrosis (CHF): A Report of Two Cases and an Overview

Congenital hepatic fibrosis is a rare, mostly autosomal recessive disorder that belongs to the group of diseases known as fibrocystic hepatic disorders. The fibrocystic hepatic disorders include Caroli’s disease, Von Meyenburg complex (multiple biliary hamartomas) and polycystic liver diseases. Disordered maturation of the ductal plates representing the embryonic skeleton of the intrahepatic biliary ducts had been acknowledged as ductal plate malformations (DPMs). These DPMs are portraying the pathogenetic background for the fibrocystic hepatic disorders. CHF had mostly been described in the context of autosomal recessive polycystic kidney disease. Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been documented in ARPKD/CHF. Fibrocystin; a transmembrane protein encoded by PKHD1 gene, is located in the renal tubular and bile duct epithelial cells and thought to be important in tubulogenesis and the three-dimensional ductal structure. Fibrocystin had been found to be lacking on the inheritable combined biliary-renal disorders.