Improvement In Liver Function Tests Research Articles

Role of the bile acid receptor TGR5 (Gpbar-1) in liver damage and regeneration

Role of the bile acid receptor TGR5 (Gpbar-1) in liver damage and regeneration

Systematic review: the effects of autologous stem cell therapy for patients with liver disease.

As morbidity and mortality from liver disease continues to rise, new strategies are necessary. Liver transplantation is not only an expensive resource committing the patient to lifelong immunosuppression but also suitable donor organs are in short supply. Against this background, autologous stem cell therapy has emerged as a potential treatment option. To evaluate if it is possible to make a judgement on the safety, feasibility and effect of autologous stem cell therapy for patients with liver disease. MEDLINE and EMBASE were searched up until July 2013 to identify studies where autologous stem cell therapy was administered to patients with liver disease. Of 1668 studies identified, 33 were eligible for inclusion evaluating a median sample size of 10 patients for a median follow-up of 6months. Although there was marked heterogeneity between studies with regards to type, dose and route of delivery of stem cell, the treatment was shown to be safe and feasible largely when a peripheral route of administration was used. Of the studies which also looked at biochemical outcome, statistically significant improvement in liver function tests was seen in 16 studies post-treatment. Although autologous stem cell therapy is a much needed possibility in the treatment of liver disease, further robust clinical trials and collaborative protocols are required.

Antioxidant Supplements Reduced Oxidative Stress and Stabilized Liver Function Tests but Did Not Reduce Inflammation in a Randomized Controlled Trial in Obese Children and Adolescents1,2

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 μg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F2-isoprostanes, F2-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, β = 23.2 (95% CI: 18.0, 28.4); ascorbic acid, β = 70.6 (95% CI: 51.7, 89.4); selenium, β = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, β = −0.11 (95% CI: −0.19, −0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [β = −0.13 (95% CI: −0.23, −0.03)], a trend toward a significant effect on aspartate aminotransferase [β = −0.04 (95% CI: −0.09, 0.01)], and no significant effect on γ-glutamyltransferase [β = −0.03 (95% CI: −0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved antioxidant–oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov> as NCT01316081.

Effects of Silymarin on Treatment Naïve Patients with Chronic Hepatitis B Infection-A Randomized Controlled Trial

Background: Silymarin, an extract of milk thistle (silybum marianum) is widely used in the treatment of patients with chronic liver disease yet its beneficial effects remain controversial. Aim: To determine the effect of silymarin on liver biochemistry and health related quality of life (HRQOL) in treatment naive patients with chronic hepatitis B infection. Methods: This was a double-blind randomized placebo-controlled trial conducted at the University of Calabar Teaching Hospital, Cross river state. Patients with chronic hepatitis B were randomized to receive silymarin or placebo for 4 weeks. Their liver function tests and HRQOL were assessed at baseline and post-treatment. Results: Eighty-six persons were enrolled into the study. Seventy-nine completed the study. Silymarin use was associated (p<0.05) with improvement in serum alanine and aspartate aminotransferase and HRQOL from baseline but not with serum bilirubin and alkaline phosphatase. Conclusion: Silymarin use among patients with chronic hepatitis B is associated with improvement in liver function tests especially markers of liver inflammation and HRQOL.

The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten-Free Diet on Diseases Improvement

ContextCeliac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet.Evidence AcquisitionPubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified.ResultsRecently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders.ConclusionsAlthough GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia.

Do All Fingers Point Towards Malignancy? Story of a Great Masquerader

Purpose: A 49-year-old man presented with dark urine, epigastric discomfort, and 20-pound weight loss in 3 months. Past medical and family history was unremarkable. He denied alcohol use. On examination, he was afebrile and hemodynamically stable, but was diffusely jaundiced with moderate epigastric tenderness. Total bilirubin/direct bilirubin was 29.3/15 mg/dL, AST/ALT 341/311 U/L, alkaline phosphotase/GGT 1928/944 IU/L, CA-19-9 >1500. Ultrasound revealed a 20-mm common bile duct (CBD) and gallbladder sludge. A computed tomography (CT) revealed severe dilation of intra- and extrahepatic bile ducts with tapering into the head of pancreas (HOP), and mild prominence of the HOP without obvious mass lesions. Differential diagnosis of malignancy and autoimmune pancreatitis/cholangiopathy were considered. Endoscopic ultrasound (EUS) revealed dilated CBD (19 mm) and dilated cystic duct (CD) 10 mm with low insertion. A single, round, hyperechoic defect (15 mm) with acoustic shadowing was noted in the distal CD causing extrinsic compression of the CBD at the level of HOP without any evidence of HOP mass lesion. Endoscopic retrograde cholangiopancreatography (ERCP) revealed non-dilated pancreatic duct and 15-mm oval filling defect in the CD causing distal CBD compression. After a biliary sphincterotomy and selective cannulation of CD, a large stone was removed using a basket. Post-procedure there was a significant improvement in liver function tests and CA 19-9 down-trended and eventually normalized in 6 weeks. Discussion: Obstructive jaundice, weight loss, and high levels of CA 19-9 along with radiologic findings of CBD narrowing are highly suggestive of pancreatobiliary malignancy. However, benign disorders such as cholelithiasis, choledocholithiasis, and autoimmune process should be considered in the differential diagnosis. This case represents typical presentation of Mirizzi's syndrome type 1B. EUS is a valuable tool for accurate diagnosis of distal biliary pathology. ERCP with stone extraction from the cystic duct is safe and effective. Elevated levels of CA 19-9 usually point to a neoplastic phenomenon; however, one must thoroughly rule out benign causes.Figure: ERCP image: cystic duct filling defect.

A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

Adenoviral Gene Transfer of Hepatic Stimulator Substance Confers Resistance Against Hepatic Ischemia–Reperfusion Injury by Improving Mitochondrial Function

Hepatic stimulator substance (HSS) has been suggested to protect liver cells from various toxins. However, the precise role of HSS in hepatic ischemia-reperfusion (I/R) injury remains unknown. This study aims to elucidate whether overexpression of HSS could attenuate hepatic ischemia-reperfusion injury and its possible mechanisms. Both in vivo hepatic I/R injury in mice and in vitro hypoxia-reoxygenation (H/R) in a cell model were used to evaluate the effect of HSS protection after adenoviral gene transfer. Moreover, a possible mitochondrial mechanism of HSS protection was investigated. Efficient transfer of the HSS gene into liver inhibited hepatic I/R injury in mice, as evidenced by improvement in liver function tests, the preservation of hepatic morphology, and a reduction in hepatocyte apoptosis. HSS overexpression also inhibited H/R-induced cell death, as detected by cell viability and cell apoptosis assays. The underlying mechanism of this hepatic protection might involve the attenuation of mitochondrial dysfunction and mitochondrial-dependent cell apoptosis, as shown by the good preservation of mitochondrial ultrastructure, mitochondrial membrane potential, and the inhibition of cytochrome c leakage and caspase activity. Moreover, the suppression of H/R-induced mitochondrial ROS production and the maintenance of mitochondrial respiratory chain complex activities may participate in this mechanism. This new function of HSS expands the possibility of its application for the prevention of I/R injury, such as hepatic resection and liver transplantation in clinical practice.

Immunoglobulin G4-Associated De Novo Autoimmune Hepatitis After Liver Transplantation for Chronic Hepatitis B- and C-Related Cirrhosis and Hepatocellular Carcinoma: A Case Report With Literature Review

Immunoglobulin G4 (IgG4)-associated autoimmune hepatitis (AIH) was recognized as a new disease entity; however, IgG4-associated de novo AIH after the liver transplantation had not been reported yet. Herein we have described a 56-year-old man who developed IgG4 de novo AIH as 1 year–post liver transplantation after receiving pegylated interferon alpha-2a and ribavirin therapy for hepatitis C virus recurrence. The histopathologic evidence showed an aggressive lymphoplasmacytic interface hepatitis with centrilobular necrosis (plasma cells > 30%) and IgG4-positive plasma cells (>10 per high power field). Serum IgG (9220 mg/dL) and IgG4 (3289 mg/dL) were also elevated. Improvement of liver function tests (LFTs) by prednisone and azathioprine therapy are manifested as normalized alanine aminotransferase and IgG levels. IgG4 relates to more severe histological activity; however, it is believed to be a good prognostic predictor of a response to prednisone plus azathioprine therapy especially with early diagnosis and timely management.

A randomized double‐blind, placebo‐controlled study of therapeutic effects of silymarin in β‐thalassemia major patients receiving desferrioxamine

Thalassemia is one of the most common genetic disorders worldwide. Chronic blood transfusions treat the underlying anemia but may lead to iron toxicity. Effective iron chelation remains one of the main targets of clinical management of thalassemia major. In this study, iron-chelating activity of silymarin, a flavonolignan isolated from silybum marianum, was examined in β-thalassemia major. Patients were treated with the combination of desferrioxamine and silymarin (Legalon(®) ; n = 49) or desferrioxamine plus placebo (n = 48) for 9 months. The serum levels of ferritin, iron, total iron-binding capacity (TIBC), soluble transferrin receptor, and hepcidin were determined at the baseline and after 9-month therapy. Liver function test was performed before and after treatment in both groups. Serum ferritin levels decreased significantly from the beginning to the end of silymarin treatment (3028.8 ± 2002.6 vs. 1972.2 ± 1250.6 ng/mL); however, no significant change in serum ferritin was observed in the patients receiving placebo (2249.0 ± 1304.2 vs. 2015.6 ± 1146.8). Moreover, serum iron and TIBC levels were significantly reduced in silymarin group compared with placebo. Patients on silymarin therapy also exhibited a significant decrease in serum levels of hepcidin and soluble transferrin receptor after 9-month treatment period. A significant improvement in liver function test was observed in silymarin group in comparison with placebo. This study shows that silymarin is effective at reducing iron overload in patients when used in conjunction with desferrioxamine. Therapeutic effects of silymarin on a background of desferrioxamine suggest the potential effectiveness of silymarin alone in reducing body iron burden.

Liver involvement in Turner syndrome

Liver test abnormalities are frequent in adult patients with Turner syndrome, corresponding to various pathophysiological mechanisms. Steatosis, steatofibrosis and steatohepatitis are the most frequently reported lesions, caused by metabolic disorders, which are commonly related to overweight. Marked architectural changes, including nodular regenerative hyperplasia, multiple focal nodular hyperplasia and cirrhosis, found in some patients, are associated with a risk of severe liver-related complications. Architectural changes are often observed and are associated with vascular disorders caused by congenitally abnormal vessels. Finally, small bile duct alterations resembling sclerosing cholangitis occur in several patients. Oestrogen replacement therapy does not cause liver toxicity in patients with Turner syndrome and is not contraindicated in case of elevated liver enzymes. Moreover, in recent studies, oestrogen therapy was reported to improve liver function tests. Because of the wide spectrum of potential liver injuries that may occur in Turner syndrome patients, a regular screening of liver enzymes is recommended for early detection and treatment.

Successful Liver Transplantation in a Patient with Imatinib Induced Fulminant Liver Failure: A Case Report and Review of Relevant Literature

Purpose: Imatinib is the first of its class of tyrosine kinase inhibitors that was approved by the FDA in May 2001 for the treatment of Chronic Myeloid Leukemia (CML). Since then it has become the first line drug for treatment of CML. One of the lesser common adverse effects of Imatinib is hepatotoxicity and it is recommended to check liver function tests (LFTs) at baseline and then every month after initiation of Imatinib therapy. The hepatitis resulting from Imatinib often reverses with cessation of therapy. Even then, there have been several case reports of fatal hepatotoxicity induced by Imatinib in patients with both CML and Gastrointestinal Stromal Tumors (GIST). We present a case report of a successful orthotopic liver transplant in a patient with CML who developed fulminant liver failure following Imatinib use. Patient is a 46-year-old female with chronic phase CML who was started on treatment with Imatinib. She responded well to treatment and developed complete cytogenetic remission and partial molecular response by week 20 of treatment. Around this time, she was enrolled in a clinical study and started on Zileuton. Subsequently, she went on a pleasure trip where she reported consuming small quantities of alcohol and also using NSAIDs for myalgias. Around week 29 of treatment, she was found to have elevated LFTs on routine oncologic follow-up. Over the ensuing 8 weeks, her condition continued to deteriorate and she developed fulminant liver failure. Investigations for other etiologies of liver failure were all negative. Liver biopsy showed hepatocyte necrosis and overall picture was consistent with drug induced liver injury. She was given a trial of oral corticosteroids but there was no improvement in LFTs. She ultimately underwent cadaveric donor orthotopic liver transplant. Her post operative course was uneventful and she had good engraftment of the transplanted liver. She is 21 months post transplant and continues to do well. From the CML standpoint, she remains in hematologic remission. In our literature search, we found only one case report where a liver transplant was attempted in a patient with Imatinib induced severe hepatic injury and acute liver failure but the patient died in the immediate post transplant period from sepsis. With increasing use of Imatinib for many more indications other than CML, we may see an increase in cases with severe Imatinib induced liver injury and failure. There is some evidence showing treatment with prednisone may help reverse the hepatocellular damage. However, in cases where prednisone fails to show a desirable response, liver transplantation remains a practical option.

Toxic hepatitis in a group of 20 male body-builders taking dietary supplements

Dietary supplements have been used for decades for enhancing muscle growth. The harm caused by some of these products is well documented. We investigated and reported toxic hepatitis in 20 male athletes following self-prescribing of a number of dietary supplements which are lesser known. The patients’ ages ranged from 24 to 32 with a mean of 28years. They had taken three kinds of supplements for 1year including testosterone optimizer agent T Bomb II, a creatine supplement Phosphagen and an amino acid based supplement Cell-Tech. Based on the history, clinical examination, and laboratory findings the cases were diagnosed as toxic hepatitis. After discontinuation of taking the supplements, clinical recovery and improvement of liver function tests were achieved within 30days. Causality assessment with the CIOMS (Council for International Organization Medical Sciences) scale showed a “possible” grade of causality (+5 points) for these supplements. It can be concluded that these newer anabolic supplements may induce toxic hepatitis. Since the health risks of them may be severe, the use of these kinds of dietary supplements should be discouraged.

Hepatic Stimulator Substance Alleviates Toxin-Induced and Immune-Mediated Liver Injury and Fibrosis in Rats

Liver fibrosis is a common scarring response to chronic liver injury. It is a precursor to cirrhosis and liver carcinoma. Hepatic stimulator substance (HSS), a known liver-specific but species-nonspecific growth factor, has been shown to protect hepatocytes from various toxins. We have investigated the effects of HSS therapy on carbon tetrachloride (CCl(4))-induced and porcine-serum-mediated hepatic injury and fibrosis. We hypothesize that HSS might attenuate liver injury and fibrosis by suppressing oxidative stress, down-regulating profibrogenic factors, and blocking HSCs activation. This report demonstrated that HSS therapy diminished α-smooth muscle actin expression, decreased intrahepatic reactive oxygen species (ROS) level, and down-regulated transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. In addition, HSS treatment significantly protected the liver from injury by improving liver function tests and histological architecture of the liver. These results provided novel insights into the mechanisms of HSS in the protection of the liver. Our results suggested that HSS might be a therapeutic antifibrotic agent for the treatment of liver fibrosis.

Portal biliopathy: imaging manifestations on multidetector computed tomography and magnetic resonance imaging

Portal biliopathy refers to biliary abnormalities secondary to extrahepatic portal vein obstruction and cavernous transformation and is caused by vascular compression from peribiliary collateral vessels, producing segmental stenoses of the common bile duct and abnormal liver function test (LFT) results.A review of imaging studies yielded 18 patients with abnormal LFT results, biliary tract dilatation, and extrahepatic portal vein obstruction with cavernous transformation. Multidetector computed tomography and magnetic resonance imaging showed biliary stenotic segments in 11 patients secondary to extrinsic compression from enlarged peribiliary collaterals. Clinical and imaging follow-up demonstrated improvement in LFT results with minimal decrease in bile duct dilatation, eliminating percutaneous or endoscopic biliary intervention.

Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: Long-term results

The combination of ursodeoxycholic acid (UDCA) and vitamin E is a therapeutic option for nonalcoholic steatohepatitis (NASH) but randomized controlled studies have produced inconsistent results. The objective of this study was to report the long-term tolerability and efficacy of this combination in our ten-year single center experience. The study group included 101 adult patients with persistent elevation of serum aminotransferases (AST and ALT) and/or γ glutamyl-transferase (GGT), in whom a histological diagnosis of NASH was made from January 1998 to January 2009, and who were treated with a combination of UDCA with vitamin E. Median body mass index (30 kg/m(2)) remained unchanged during the study. UDCA and vitamin E were well tolerated (5% withdrawal for side effects). Mean serum AST, ALT and GGT levels (expressed as times of Upper Normal Limit) diminished significantly (1.39 ± 0.74 to 0.78 ± 0.34 for AST, 1.72 ± 0.92 to 0.91 ± 0.69 for AST and 3.25 ± 2.85 to 1.30 ± 1.30 for GGT). AST, ALT and GGT reached normal range in 80%, 70% and 65% of the patients, respectively. From the ten patients who had a second liver biopsy during follow-up, NAS score improved in seven, and worsened in one. The combination of UDCA with vitamin E significantly improves liver function tests in long-term and is very well tolerated.

Phase II Trial: Undifferentiated Versus Differentiated Autologous Mesenchymal Stem Cells Transplantation in Egyptian Patients with HCV Induced Liver Cirrhosis

The study was aimed to evaluate the effect of autologous transplantation of BM-derived undifferentiated and differentiated MSCs in cirrhotic patients following chronic hepatitis C virus infection. Twenty-five patients with Child C liver cirrhosis, MELD score >12 were included. They were divided into 2 groups. Group I, the MSCs group (n=15), this group was subdivided into two subgroups: Ia & Ib (undifferentiated and differentiated respectively). Group II (control group; n=10) involved patients with cirrhotic liver under conventional supportive treatment. Ninety ml BM was aspirated from the iliac bone for separation of MSCs. Surface expression of CD271, CD29 and CD34 were analyzed using flowcytometry. Hepatogenesis was assessed by immunohistochemical expression of OV6, AFP and albumin. Finally approximately 1 million MSCs/Kg were suspended in saline and were placed in blood bag and injected slowly intravenously over 15 min at a rate of 5 drops/min in one session. Follow up of patients at 3 and 6 months postinfusion revealed partial improvement of liver function tests with elevation of prothrombin concentration and serum albumin levels, decline of elevated bilirubin and MELD score in MSCs group. Statistical comparisons between the two subgroups (group Ia & Ib) did not merit any significant difference regarding clinical and laboratory findings. Bone marrow MSCs transplantation either undifferentiated or differentiated can be used as a potential treatment for liver cirrhosis.

A Unique Case of Autoimmune Hepatitis Developing in a Patient with Kikuchi-Fujimotoʼs Disease

Purpose: We describe a 35 year old Hispanic woman with Kikuchi-Fujimoto's disease (KFD) who developed jaundice; abnormal liver function tests (LFTs) and was found to have developed autoimmune hepatitis (AIH). KFD (histiocytic necrotizing lymphadenitis) is a rare condition of unknown etiology first described in 1972 independently by Kikuchi and Fujimoto. It is a nonmalignant disease characterized by fever and cervical adenopathy and has a self-limiting course. This is the first reported case of a patient with histologically confirmed KFD developing AIH. One prior case report has described KFD occurring after AIH. A 35 year old Hispanic female was referred to our hepatology clinic due to complaints of worsening fatigue and jaundice for two weeks. Her past medical history was significant for KFD diagnosed 14 months ago via cervical lymph node biopsy. She was not on any treatment. On examination, the patient's vital signs were stable and she was afebrile. Abdominal examination was significant for mild tenderness in the right upper quadrant without any guarding or rigidity. Pertinent abnormal laboratory data included Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) 1122/1247 U/L, Alakaline phosphatase 213 U/L, Gammaglutamyl transferase 216 U/L, total bilirubin 5.7 mg/dl, conjugated bilirubin 3.6 mg/dl, total protein 8.5 g/dl, albumin 3.3 g/dl, elevated Immunoglobulin G (IgG) level 2450 mg/dl and anti-smooth muscle antibody positive 1:640. The complete blood count, serum chemistry, viral hepatitis serologies, iron panel, ferritin, ceruloplasmin, alpha one antitrypsin, anti-nuclear antibody, anti-mitochondrial antibody and tissue-transglutaminase antibody were normal. Liver ultrasound was suggestive of mild diffuse fatty infiltration. A liver biopsy was performed which showed lymphoplasmacytic infiltrates, interface hepatitis, grade 4/4 inflammation, stage 2/4 fibrosis. The patient was diagnosed with AIH based on the clinical presentation, laboratory data and the biopsy results. The pre-treatment AIH score was 18. The patient was started on prednisone 60 mg orally daily for one week and there was significant improvement in LFTs. The steroid dose was tapered in the following weeks and the patient was noted to have complete normalization of LFTs and IgG by the fifth week of therapy. Azathioprine 75 mg daily was added with the tapering of the prednisone dose. Six months post-diagnosis, the patient is asymptomatic on a maintenance dose of prednisone 5 mg and azathioprine 75 mg daily. The coexistence of KFD and AIH is extremely rare in the reported literature. Our case is unique as it is the first reported case of histologically confirmed KFD who developed jaundice and was subsequently found to have AIH.

A patient with a metastatic gastroenteropancreatic endocrine carcinoma causing hyperinsulinaemic hypoglycaemia and the carcinoid syndrome

We present the case of a 57-year-old patient who initially presented with a constellation of symptoms including intense pruritis, flushing and diarrhoea. Following several months clinical deterioration, the patient was investigated radiologically, where multiple hepatic tumours were identified. Liver biopsy confirmed the presence of a well-differentiated metastatic gastroenteropancreatic endocrine carcinoma with biochemical evidence of serotonin secretion. Over a period of six months, the clinical course of the patient's disease progressed whereby severe hypoglycaemia became the major manifestation. Subsequent biochemical investigations confirmed the diagnosis of an insulinoma. Extensive radiological investigation revealed a solitary primary pancreatic tumour, indicating the presence of a metastatic pancreatic endocrine tumour (PET) secreting both insulin and serotonin. The patient was treated with a chemotherapy regimen consisting of 12 cycles of 5-fluorouracil/oxaliplatin, responding clinically - improved World Health Organization performance score from 3 to 1, biochemically - significantly reduced plasma chromogranin A and cancer antigen 19-9 concentrations and improved liver function tests, and radiologically - reduced pancreatic and hepatic tumour size. This is the first report of a primary PET secreting insulin and serotonin. Due to the association of serotonin-secreting gastroenteropancreatic endocrine tumours (GEP-ETs) with multiple endocrine neoplasia type-1 (MEN1) and biochemical evidence of an insulinoma, MEN1 should also be considered in such cases. The case provides further evidence for the biological heterogeneity of GEP-ETs and the myriad secretory humoral products and resultant clinical syndromes arising from such tumours.

Therapeutic Effects of Korean Red Ginseng Extract in Egyptian Patients with Chronic Liver Diseases

Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.