Urinary abnormalities in children and adolescents with Wilson disease before and during treatment with d-penicillamine.

BACKGROUND AND AIM: Renal abnormalities can occur at any time point during the course of Wilson disease (WD). We aimed to fill a literature gap in this respect by studying urinary abnormalities in children and adolescents with WD. METHODS: This study included 60 children with WD presenting to the Pediatric Hepatology Unit, Cairo University. The following data were retrieved from the patients' files including age, sex, liver function tests, serum ceruloplasmin, 24-h urinary copper, serum creatinine, blood urea nitrogen, urinalysis, urinary albumin/creatinine ratio, urinary calcium/creatinine ratio, urinary ß2-microglobulin, liver and renal biopsy results when available. RESULTS: All studied cases had no symptoms related to renal involvement. Microscopic hematuria was detected in 11% and 12% at baseline and within 5 years of therapy, respectively. Moderate microalbuminuria was detected in 34%, 50%, and 33% at baseline, within 5 years and > 5 years after therapy, respectively. Hypercalciuria was detected in 23% at baseline, 34% in those patients treated for up to 5 years and 37.5% > 5 years of therapy. Age and international normalized ratio were significantly higher in patients with high calcium/creatinine ratio compared with those with normal values at initial evaluation. Frequency of elevated urinary ß2-microglobulin was 36%, 36%, and 37% in patients at baseline, up to 5 years and > 5 years of therapy, respectively. CONCLUSION: Asymptomatic urinary abnormalities are present in patients with WD at any time point of the disease and during treatment with d-penicillamine. They have to be searched for, as early intervention may prevent progression to renal insufficiency.

Copper concentrations in Egyptian infants with cholestasis: A single center study.

BACKGROUND AND STUDY AIMS: Hepatobiliary cholestatic disorders produce excess copper (Cu) retention in the liver, which is toxic and may cause hepatitis, fulminant hepatic failure, cirrhosis and death. In this study, we measured hepatic Cu and tested its correlation with serum Cu (S. Cu) and serum ceruloplasmin (S. ceruloplasmin) in cholestatic infants. PATIENTS AND METHODS: 41 cholestatic infants were enrolled as cases and 11 healthy infants as control subjects. S. Cu and S. ceruloplasmin were done for all infants and hepatic Cu was measured in the liver specimen in cases. RESULTS: Cases were 63.5% males with their age ranging between 1 and 7 months, while control subjects were 45.5% males with an age range between 3 and 18 months. Among cases, 41.5% had biliary atresia and 58.5% had intrahepatic cholestasis. Cholestatic infants had significantly higher levels of S. Cu and S. ceruloplasmin than control subjects and their hepatic Cu concentration was significantly higher than literature control. Infants with biliary atresia showed higher levels of Cu indices, with no statistical significance. Serum and hepatic Cu levels positively correlated with each other and with S. ceruloplasmin. Results of ROC curve showed that S. Cu was highly sensitive and specific for predicting hepatic Cu concentration at cut-off 181 µg/dl. CONCLUSION: Serum and hepatic Cu concentrations were markedly elevated in patients with cholestasis and positively correlated with each other and with S. ceruloplasmin. S. Cu level can predict hepatic Cu concentration.

Ocular findings in patients with cholestatic disorders of infancy: A single-centre experience.

BACKGROUND AND STUDY AIMS: Neonatal cholestasis can be associated with ocular findings that might aid in its diagnosis, e.g., Alagille syndrome (AGS) and Niemann Pick disease (NPD). We aimed to investigate the frequency of ocular manifestations in infants with cholestasis. PATIENTS AND METHODS: This cross-sectional study included cholestatic infants presenting to the Paediatric Hepatology Unit, Cairo University Paediatric Hospital, Cairo, Egypt. All infants underwent examination of lid, ocular motility, anterior and posterior segments and measurement of intraocular pressure, cycloplegic refraction, ocular ultrasonography and vision. RESULTS: The study included 112 infants with various cholestasis; 73 (65.2%) were males. The median age was 2months. Diagnosis was reached in 39 cases: 14 had AGS, 14 had biliary atresia (BA), 4 had NPD, 4 had post-haemolytic cholestasis, 2 had cytomegalovirus neonatal hepatitis, and one case had hepatorenal tyrosinaemia. Thirteen cases were probably having progressive familiar intrahepatic cholestasis (PFIC) type 1 or 2 considering their persistent cholestasis in the presence of normal gamma-glutamyl transpeptidase; 28 were left with a diagnosis of "idiopathic neonatal hepatitis" (INH), and 32 (28.6%) had no definite diagnosis. Ophthalmologic abnormalities were found in 39 cases (34.8%). The commonest finding was unilateral/bilateral optic nerve drusen in 12 (10.7%), followed by posterior embryotoxon in 11 (9.8%). Ocular findings were observed in 64.3% patients with AGS, 50% patients with NPD, 30.8% cases with suspected PFIC type 1or 2, 28.6% infants with INH, and 14.3% patients with BA. CONCLUSION: Ophthalmologic findings are not uncommon among cholestatic infants. Ophthalmologic examination should be routinely performed, including assessment of anterior segment, fundus examination, and ocular ultrasound.

Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis.

Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 µg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.

Extrahepatic portal vein obstruction in Egyptian children.

BACKGROUND AND AIM: Extrahepatic portal vein obstruction (EHPVO) is an important cause of portal hypertension in children. The aim of this study was to describe the clinical presentation, possible risk factors, upper gastrointestinal endoscopic findings, and treatment modalities of children with EHPVO. METHODS: After ethical approval of our study protocol by our institution review board, we analyzed available data from medical records of patients with EHPVO presenting to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt, for a period of 15 years from January 1996 to December 2010. RESULTS: The study included 169 patients. Their ages at presentation ranged from 1 month to 12 years (median 2.5 years, interquartile range 5); 101 were boys. Hematemesis was a presenting symptom in 58%, splenomegaly was present in 87%, esophageal varices were present in 94%, and fundal varices were present in 23%. Possible risk factors, in the form of umbilical catheterization, umbilical sepsis, and exchange transfusion, were elicited in 18%. Propranolol was associated with reduction in bleeding episodes (P < 0.001), but was associated with increased chest symptoms (P < 0.01). Both injection sclerotherapy and band ligation were effective in the management of bleeding varices and for primary and secondary prophylaxis; however, injection sclerotherapy was associated with the development of secondary gastric varices (P = 0.03). CONCLUSIONS: This large study of children with EHPVO demonstrates the efficacy of propranolol in the reduction of gastrointestinal bleeding in children with EHPVO. Both injection sclerotherapy and band ligation were effective in the management of esophageal varices, although the former was associated with the development of secondary gastric varices. Randomized clinical trials to choose the best modalities for the management of portal hypertension in children are still lacking.

Gene mutations in Wilson disease in Egyptian children: report on two novel mutations.

BACKGROUND AND STUDY AIMS: Wilson disease (WD) is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase (ATPase) encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation (p.H1069Q) in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group. PATIENTS AND METHODS: Direct DNA sequencing was applied to exons (13, 14, 18, and 19) of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families (three families). RESULTS: We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution (p.A1074A) in 16% of patients and the other was predicted to be missense disease-causing mutations (p.T1076I) in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients. CONCLUSION: Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations.

Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children.

AIM: To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection. METHODS: Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493). RESULTS: Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well. CONCLUSION: Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Assessment of coagulation and fibrinolysis in children with chronic liver disease.

We aimed at assessing the coagulation profile and detecting early evidence of fibrinolysis in pediatric patients with chronic liver disease. Seventy-six patients (40 boys) with a mean age of 9.8 ±â€Š3.4 years suffering from chronic liver disease were enrolled in this study. They were followed up in the Pediatric Hepatology Unit, Cairo University Children's Hospital. Thirty healthy children were included as controls. Patients were classified etiologically into four groups: chronic viral hepatitis, autoimmune hepatitis, miscellaneous and cryptogenic groups. Investigations to detect coagulopathy were done for all patients and controls: prothrombin time (PT), activated partial thromboplastin time, fibrinogen, fibrinogen degradation products, and D-dimer and complete blood count. Liver functions were done for all patient groups. A significantly lower platelet count, prolonged prothrombin time, with prolonged aPTT time was detected in all patients compared with controls (P < 0.001). The fibrinogen level showed no significant difference between patients and controls. D-dimer level was significantly higher in the miscellaneous and cryptogenic groups when compared to other patient groups and control group (P < 0.001). Significantly higher D-dimer levels were detected in patients with liver cirrhosis of child class A and B compared with noncirrhotic and control groups (P < 0.001). D-dimer correlated positively with PT (r = 0.290, P = 0.003), and negatively with platelet count (r = -0.324, P = 0.001) and prothrombin concentration (r = -0.270, P = 0.018). Fibrinolytic activity, as evidenced by high D-dimer, was detected in pediatric patients with chronic liver disease particularly if cirrhotic.

Ultrasonography as a non-invasive tool for detection of nonalcoholic fatty liver disease in overweight/obese Egyptian children.

INTRODUCTION: Liver biopsy, although a gold standard in diagnosis of nonalcoholic fatty liver disease (NAFLD), is an invasive and expensive tool. AIM: To assess the diagnostic accuracy of abdominal ultrasound in detecting NAFLD among a group of overweight/obese children having one or more liver abnormality (clinical hepatomegaly, raised ALT or echogenic liver parenchyma by ultrasound). METHODS: Seventy-eight overweight/obese children were referred to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt, for assessment for hepatic abnormalities. Out of the 78 children, 34 had one or more abnormality in the form of clinical hepatomegaly, raised alanine aminotransferase (ALT) and/or echogenic liver parenchyma by ultrasound. All 34 cases underwent liver biopsy for evaluation for NAFLD. RESULTS: Histological NAFLD was detected in 15 cases; 8 simple steatosis and 7 nonalcoholic steatohepatitis (NASH). Sonographic evaluation of hepatic parenchymal echogenicity revealed: 11 with grade 1 echogenicity, 12 with grade 2 and 9 with grade 3 while only 2 had normal liver echopattern. Ultrasonography was 100% sensitive and 100% specific in detecting histological NAFLD, while the positive predictive value (PPV) was 47% and negative predictive value (NPV) was 11%. After consolidating the included children into 2 groups: the first including normal and grade 1 echogenicity and the second including grades 2 and 3, the sensitivity of ultrasonography in detecting histological NAFLD was still 100%, while negative predictive value increased to 100% with an accuracy of 82%. CONCLUSION: We conclude that ultrasonography is an important non invasive tool in assessment for NAFLD. Normal or grade 1 hepatic echogenicity can soundly exclude histological NAFLD and obviates the need for liver biopsy.

Patterns of hepatitis B infection in Egyptian children in the era of obligatory hepatitis B vaccination.

BACKGROUND AND STUDY AIMS: Mass compulsory HBV vaccination was applied in Egypt in 1992. The first dose of vaccine is administered at 2 months of age and routine screening of pregnant women for HBsAg is not applied. We aimed to evaluate the pattern of HBV infections after the implementation of HBV vaccination in Egyptian children. PATIENTS AND METHODS: Fifty-six children with HBV infection presented to the Paediatric Hepatology Unit, Cairo University Children's Hospital, over the period from 1992 to 2006. Their data were reviewed for risk factors, clinical, serological and histopathological profiles. These cases were followed-up for 6.3 ± 3.4 years. The data of those born before 1993 (did not receive HBV vaccine) (group I) was compared to those who received the vaccine (group II). RESULTS: Sixty percent of HBV infected cases were born before 1993. Comparison of data of both groups revealed: (1) A significant younger age of onset in group II (3.34 ± 3.31 years vs. 9.84 + 2.95 years; p ≤ 0.01). (2) Vertical transmission was a significant risk factor in group II. (3) Chronic hepatitis developed in almost half of cases in both groups but cirrhosis was diagnosed only in 4 cases (all from group I) (p=0.04). CONCLUSION: Vertically transmitted HBV infection is becoming an important risk factor for acquisition of HBV among children born after the era of mass vaccination in Egypt. Mass screening for HBsAg of pregnant Egyptian women and/or giving a birth dose of HBV vaccine is becoming mandatory with the increased incidence of vertical transmission.

The association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children.

BACKGROUND/AIM: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). PATIENTS AND METHODS: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. RESULTS: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). CONCLUSION: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.

Relation of serum levels of thrombopoietin to thrombocytopenia in extrahepatic portal vein obstruction versus cirrhotic children.

INTRODUCTION: In patients with portal hypertension, thrombocytopenia in cirrhotics and noncirrhotics is thought to be caused by sequestration and destruction of platelets within a large spleen, suppression of platelet production in the bone marrow, and decreased activity of the hematopoietic growth factor thrombopoietin (TPO). AIM: Determining the level of TPO in cirrhotic thrombocytopenic patients and correlate it to the degree of disease severity and platelet count. METHODS: A cross-sectional study conducted on 62 children; 25 cases with cirrhosis, 20 patients with extrahepatic portal vein obstruction (EHPVO), and 17 healthy age-matched and sex-matched controls. The severity of liver cirrhosis was graded according to the Child-Pugh classification. TPO was measured using the quantitative human TPO by enzyme-linked immunosorbant assay. RESULTS: Serum TPO levels were significantly lower in the cirrhotic group compared with both EHPVO patients and healthy controls (P=0.01 for each). Both of the Child-Pugh B and C cirrhotic cases had significantly lower TPO levels compared with Child A cases (P=0.003). We found a significant positive correlation between platelet count and serum TPO level (r=0.56, P=0.004) in the cirrhotic group but not in the EHPVO group (r=0.1, P>0.05). CONCLUSIONS: TPO underproduction contributes to thrombocytopenia in children with cirrhosis; whereas in children with EHPVO, TPO production is unaffected and thrombocytopenia is secondary to hypersplenism. TPO receptor agonists may be useful to improve platelet counts in the former group.

Strong hepatitis C virus (HCV)-specific cell-mediated immune responses in the absence of viremia or antibodies among uninfected siblings of HCV chronically infected children.

BACKGROUND: Cell-mediated immune (CMI) responses to hepatitis C virus (HCV) antigens in adults without seroconversion or viremia are biomarkers for prior transient infection. We investigated HCV-specific CMI responses in seronegative children living with HCV-infected siblings. METHODS: Children 3-18 years of age living with HCV-infected siblings were screened for HCV antibodies and HCV RNA. Peripheral blood mononuclear cells (PBMCs) were evaluated for HCV-specific CMI responses by interferon γ (IFN-γ) enzyme-linked immunospot assay using 3 recombinant HCV protein antigens. Flow cytometry phenotypically characterized IFN-γ-secreting cells. RESULTS: Forty-five seronegative children and 5 seropositive viremic siblings had functionally viable PBMCs. Among the 45 seronegative siblings, 15 (33.3%) had positive HCV-specific IFN-γ responses, and subsequent RNA testing revealed that 3 were viremic. Compared with the 5 seropositive viremic children, the median number of HCV-specific spot-forming units was significantly higher in the 12 seronegative aviremic children (P = .002) and in the 3 seronegative viremic children (P = .025). Flow cytometric analysis revealed that IFN-γ was synthesized mainly by CD4(+) T cells. CONCLUSION: Strong HCV-specific CD4(+) T cell responses were detectable in higher frequency among seronegative, aviremic children compared with persistently infected siblings. Further studies are needed to determine whether these immune responses are protective against HCV infection.

Can aspartate aminotransferase to platelet ratio index replace liver biopsy in chronic hepatitis C?

BACKGROUND AND AIM: We aimed to evaluate the accuracy of readily available laboratory tests (ALT, AST, platelet count, AST to platelet ratio index: APRI) in predicting liver fibrosis in chronic hepatitis C, in comparison to the predictive accuracy obtained by liver biopsy. Pediatrics, METHODS: One hundred and thirteen patients suffering from chronic hepatitis C (CHC) were included in this study. They included 76 children enrolled from the Pediatric Hepatology Unit and 37 adults enrolled from the Hepatology Unit of Tropical Medicine Department, Cairo University, Egypt. Fibrosis results obtained from liver biopsy were assigned a score from 0 to 4 score as per Metavir scoring. Results of serum ALT and AST levels were expressed as ratio of the upper limit of normal (ULN). RESULTS: Of the pediatric patients, 28 (36.8%) showed no evidence of fibrosis on liver biopsy, 26 (34.2%) showed grade 1 fibrosis, and 22 (29%) had grade 2 fibrosis. Among the adult patients, 12 (32.4%) had grade 2 fibrosis and 25 patients (67.6%) had grades 3 to 4 fibrosis. There was a lack of correlation between the degree of fibrosis and AST levels, AST/ALT ratio, platelet count and APRI. The AUROC curve for predicting significant fibrosis was 0.5 for AST levels, 0.37 for AST/ALT ratio and 0.49 for APRI, in pediatric patients (p > 0.05). In adult patients the AUROC curve for predicting significant fibrosis was 0.59 for AST levels, 0.76 for AST/ALT ratio and 0.63 for APRI (p > 0.05). CONCLUSION: Liver biopsy remains the gold standard to assess the extent of hepatic fibrosis in patients with CHC.

Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus.

BACKGROUND AND AIM: Children with type 1 diabetes mellitus (T1DM) are frequently investigated for hepatic abnormalities. This study was carried out to report on the prevalence of hepatic abnormalities in diabetic children and adolescents and to highlight the possible etiology and appropriate management. METHODS: The study included 692 children (333 were males) with T1DM attending the Diabetes Unit at Cairo University Pediatric Hospital. Their mean age was 9.65 ± 4.18 yr. All children were subjected to clinical examination for hepatomegaly, determination of alanine aminotransferase (ALT) and antibodies to hepatitis C virus (anti-HCV), and abdominal ultrasonography. All children with clinical, laboratory or ultrasound abnormality were counseled about proper glycemic control and followed up. If abnormalities persisted, more detailed investigations were carried out. HCV RNA was done for anti-HCV positive children. RESULTS: Sixty (8.7%) were found to have one or more abnormalities: clinical hepatomegaly in 13 (1.9%), elevated ALT in 27 (3.9%), anti-HCV in 25 (3.6%) and abnormal hepatic ultrasound in 31 (4.5%). Forty percent of anti-HCV positive children were HCV-RNA positive. Glycogenic hepatopathy was diagnosed in three cases by liver biopsy. Abnormalities were reversible in 37/60 after proper glycemic control. CONCLUSION: Although diabetic children are at risk of acquisition of HCV, poor glycemic control is the key factor that predisposes to hepatomegaly, elevated ALT and abnormal ultrasound findings. A 4 to 8-wk therapeutic trial of proper glycemic control is recommended prior to more invasive diagnostic procedures.