Improvement In Liver Function Tests Research Articles

Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats.

Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. LPS group showed higher levels of fibrosis and collagen content stained by Masson's trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (p<0.05). Treatment by TQ restored liver fibrosis, improved liver function tests and increased the levels of anti-oxidative enzymes (SOD and catalase), while reduced MDA concentration (p<0.05). Treatment by TQ restores inflammation-induced liver fibrosis possibly through affecting oxidative stress status. It seems that administration of TQ can be considered as a part of liver fibrosis management.

Neonatal Hypopituitarism: Unusual Presentation

Objective We report an infant with panhypopituitarism presenting with cholestatic jaundice, hypoglycemia, and high ferritin level. Methods We conducted clinical and laboratory investigations, including metabolic, infectious, and hormonal evaluation. Results Hormonal evaluation revealed panhypopituitarism (cortisol deficiency, growth hormone deficiency, and central hypothyroidism). Other causes of cholestasis were ruled out. Surprisingly, serum ferritin level was very high suggesting neonatal hemochromatosis, which was ruled out by the absence of hemosiderin deposition in buccal mucosal biopsy. Replacement therapy with glucocorticoids and L-thyroxin showed improvement of liver function tests, resolved cholestatic jaundice, and significantly decreased serum ferritin level. These findings support the assumption that thyroid hormone and cortisol affect the bile acid-independent bile flow. Conclusion This is the first description of an infant with congenital panhypopituitarism, presenting with cholestasis, hypoglycemia, and high serum ferritin level. Panhypopituitarism should be considered in any infant who presents with cholestasis, hypoglycemia, and other manifestations of pituitary malfunction. High serum ferritin level probably reflects acute phase reaction.

Pre-operative Hepatic Artery Resistive Index is a Non-invasive Predictive Indicator of Prognosis in Biliary Atresia.

Aims:The aim of this study is to evaluate hepatic artery resistive index (HARI) as a noninvasive prognostic predictor by correlating it with peripheral blood nitric oxide (NO) levels, portal pressure (PP) and histopathological changes in the liver in patients of biliary atresia (BA).Materials and Methods:Twenty-five patients were included in the study prospectively from November 2012 to June 2014. All patients underwent Doppler sonography to calculate the HARI preoperatively. Peripheral blood NO was also measured preoperatively. Biochemical liver function tests (LFTs) were measured preoperatively and at 1, 3, and 6 months postoperatively. The PP was measured intraoperatively, and a liver biopsy was taken in all patients. Disappearance of jaundice defined successful surgical treatment. Postoperatively, a hepatobiliary IminoDiacetic Acid scan (HIDA) was done to demonstrate a patent bilio-enteric pathway.Results:The mean preoperative HARI was 0.78 ± 0.105, and the median was 0.80 (range 0.60–1.0). The median HARI was used to correlate the other parameters; 13 (52%) patients had HARI ≥0.8. The mean PP was 24.96 ± 6.54 mmHg. The HARI had a strong correlation with PP (P = 0.0001) and (NO) (P = 0.0001); with every 0.1 increase in HARI, there was 5.2 mmHg increase in PP and 3.8 μmol/L increase in NO. The histological parameters which reached significance in relation to HARI were hepatocellular damage, bile duct inflammation, portal inflammation, and portal fibrosis. The postoperative improvement in LFT was significantly better in patients with HARI <0.8. All four patients who died during or after the study period had HARI >0.8, elevated PP, and NO levels.Conclusions:Preoperative HARI was found to have a direct correlation with PP and peripheral blood NO as a measure of portal hypertension. A preoperative HARI ≥0.8 should be considered as a risk factor for poor outcomes in BA.

Efficacy and safety of hepano tablet in liver disorder patients with abnormal liver function test: A randomized active controlled prospective clinical study

Objective: Hepano Tablet is an Ayurvedic herbal formulation studied in pre-clinical models for safety and hepatoprotective efficacy. The current study was a randomized, active controlled, multicentre, prospective clinical study that aimed to evaluate hepatoprotective efficacy and safety of Hepano Tablets. Materials and Methods: Male and female liver diseases patients (18-65 years) with abnormal liver function tests were randomized to receive two tablets twice daily orally of either Hepano or a marketed comparator for 8 weeks with follow up at day 7, 14, 28 & 56 during treatment period and thereafter at day 84. Results were assessed from baseline to end of treatment basis changes in liver function tests and improvement in clinical symptoms of icterus in both the groups. Safety was assessed at all the visits basis changes in laboratory parameters and adverse event reporting for all cases who took at least one dose of the study drug. Results: Hepano Tablet and marketed comparator showed significant improvement in Liver functions - Serum Aspartate transaminase (AST), Alanine transaminase (ALT) and Total, Direct and Indirect Bilirubin Levels and a significant reduction in clinical symptoms of icterus that was comparable at all the visits. Conclusion: Hepano Tablets can significantly improve Liver Function Tests and clinical symptoms in liver disease patients and could be consumed safely.

Hemorrhagic Cystitis in a Liver Transplant Recipient Secondary to BK Virus

Introduction: Solid organ transplant recipients are at increased risk of infections. Knowledge of clinical presentation and risk factors allows early diagnosis and directed therapy. We present the case of a 53-year-old liver transplant recipient male who developed hemorrhagic cystitis due to BK virus while undergoing treatment for acute cellular rejection. Case Description: Our patent is a 53-year-old male who underwent liver transplantation for cirrhosis secondary to hepatitis C. He was treated for hepatitis C post-transplant and achieved Sustained Virologic Response (SVR). The patient also had a history of Chronic Kidney Disease Stage 3. He was hospitalized for worsening liver function tests 2 years after his transplant. A liver biopsy revealed acute cellular rejection (ACR). He was treated with high dose IV steroids followed by oral taper and dual immunosuppression therapy with tacrolimus and mycophenolate. Owing no improvement in liver function tests, a repeat liver biopsy was done and showed findings consistent with severe rejection. The patient was given a second cycle of high dose IV steroids followed by 4 doses of antithymoglobulin antibody. He responded to the treatment with improvement in liver function tests, however developed gross hematuria with bladder spasms. Urine analysis showed moderate blood and pyuria. Urine cultures were negative. Treatment with broad-spectrum antibiotics failed to improve his symptoms. Cystoscopy showed diffusely inflamed bladder with no masses identified. High titers of BK virus (>5,000,000 copies /ml) were identified in urine and low level viremia was also noted by blood PCR (1,200 copies /ml). Adenovirus, another agent responsible for cystitis in immunocompromised induvial was ruled out by negative PCR. Supportive care with IV hydration and pain control resulted in gradual resolution of symptoms over two weeks. As patient was being treated for ACR, immunosuppression regimen was not changed. Kidney functions remained stable throughout hospitalization. Discussion: Cystitis secondary to viruses like BK and adenovirus has been described in renal and allogeneic hematopoietic cells transplantation. Presentation in liver transplant recipients, either at time of transplantation or during treatment of cellular rejection has not been well documented. Our case suggests that BK virus infection should be considered as the potential cause of cystitis in solid organ transplant recipients.

A Case of Secondary Sclerosing Cholangitis in the Setting of Non-Hodgkinʼs Lymphoma

Introduction Sclerosing cholangitis represents a spectrum of cholestatic liver disease characterized by inflammation, fibrosis and stricture of the bile ducts. Magnetic resonance cholangiopancreatography (MRCP) typically shows multifocal strictures and dilatation of intra and extra-hepatic bile ducts displaying a “beaded” appearance. We present a case of secondary sclerosing cholangitis in the setting of anaplastic large cell lymphoma. Case Presentation A 67-year-old Caucasian female with a past history of recurrent breast cancer status post lumpectomy, radiation and hormonal therapy, presented with jaundice and an exophytic mass at the base of tongue. Laboratory data revealed ALP 953 U/L, total bilirubin 7.7 mg/dL, direct bilirubin 6.4 mg/dL, GGT 3369 U/L, albumin 3.1 g/dL, protein 6.9 g/dL, AST 195 U/L, ALT 149 U/L. A CT scan of the chest, abdomen and pelvis showed wide spread lymphadenopathy in the chest, abdomen and pelvis concerning for lymphoma, acute pancreatitis and biliary dilation with hyper enhancement of the common bile duct wall. An MRCP was performed which showed diffuse intrahepatic biliary ductal dilatation with non-visualization of the common hepatic duct bifurcation. Diffuse narrowing with multifocal stenosis of the proximal and distal aspects of the common bile duct was also seen. Findings were consistent with sclerosing cholangitis. Pathology of the oral lesion revealed ALK1+ anaplastic large cell lymphoma. Chemotherapy was initiated with cyclophosphamide, doxorubicin, adriamycin, vincristine, etoposide, and prednisone (CHOEP-14), and resulted in significant improvement in liver function tests. Patient continued to improve clinically and was discharged with close outpatient follow up. Discussion Previous reports have suggested that only 0.2 to 2.0 % of patients with NHL have biliary tract obstruction. The diagnosis of extra-hepatic bile duct obstruction related to lymphoma is challenging when it occurs as an initial presentation. The cholangiographic appearance of these lesions can resemble benign stricture, primary sclerosing cholangitis, cholangiocarcinoma, pancreatic carcinoma, or metastatic carcinoma. NHL as a secondary cause of sclerosing cholangitis has rarely been reported in literature. It is essential for gastroenterologists, oncologists and radiologists to recognize scelorsing cholangitis occurring secondary to systemic disease, as early initiation of treatment can improve clinical outcome, as happened in our case.Figure 1Figure 2

Endoscopic Ultrasound-Guided Fine Needle Core Liver Biopsy Using a Novel 19 G Needle with a Modified Wet Suction Technique in Patients with Abnormal Liver Function Tests: 2016 ACG Presidential Poster Award

Introduction: Endoscopic Ultrasound-guided Fine Needle Core Biopsy has proven to be safe and effective technique for diagnosis of focal liver lesions. However, data are limited in its role in parenchymal disease. We evaluated the utility of EUS-guided parenchymal liver biopsies (LB) and documented adverse events (AE) using a novel 19G needle (Sharkcore, Medtronic) with a modified wet suction technique in patients (pts) referred for abnormal liver function tests (LFTs).Figure 1Figure 2Figure 3Methods: This was a single-center retrospective study of pts with unexplained abnormal LFTs who were referred for EUS of elevated LFTs to evaluate for biliary obstruction and pancreatic pathology. EUS-LB was performed at the same session after biliary obstruction was excluded. EUS-LB was performed using a modified wet suction technique. The needle was primed with saline and maximal suction was used. A rapid-puncture technique was used to sample each lobe for a total of one pass per lobe. Acquired tissue was placed into formalin, then stained with Hematoxylin and Eosin, Trichrome, and iron. The specimen length was assessed grossly and the number of complete portal triads (CPT) was determined on microscopic examination. Results: 105 consecutive pts underwent EUS-LB and data were retrospectively evaluated. Median age was 52 years (21-81) and 48 (45%) were male. The main indication was elevated LFTs with no signs of biliary obstruction, and absence of pancreas pathology during EUS. Adequacy of specimen for diagnosis was obtained in 100% of cases. Two pts previously underwent percutaneous LB, which were nondiagnostic. 25% of pts had undergone MRI elastography to assess degree of fibrosis. EUS-LB changed the fibrosis score in 54% of these pts, and altered the treatment course. The average maximum core tissue length was 2.5 cm, with a median of 16 CPT (7-35). Abdominal pain occurred in 35 pts (33.3%) immediately post-procedure, which resolved in all pts after intravenous administration of a low-dose narcotic. There was one early adverse event; a patient presented within 48 hours to the emergency room with worsened LFTs and abdominal pain. CT was normal and there was improvement in LFTs and abdominal pain in less than 24 hours. Conclusion: EUS-LB using a new needle proved to be safe with a low AE rate, and produced adequate samples measured by number of CPT and tissue specimen length. Diagnostic yield was achieved in 100% of patients and changed patient management in 12% of pts, with alteration in prior MRI fibrosis scores in half.

Insulin-Like Growth Factor I (IGF-I) Expressed from an AAV1 Vector Leads to a Complete Reversion of Liver Cirrhosis in Rats

IGF-I modulates liver tissue homeostasis. It is produced by hepatocytes and signals within the liver through IGF-I receptor expressed on hepatic stellate cells (HSCs). Liver cirrhosis is characterized by marked IGF-I deficiency. Here we compared the effect of two different gene therapy vectors encoding IGF-I as a potential treatment for cirrhotic patients. Rats with carbon tetrachloride-induced liver cirrhosis were treated with controls or with adeno-associated virus 1 (AAV) or simian virus 40 (SV40) vectors expressing IGF-I (AAVIGF-I or SVIGF-I) and molecular and histological studies were performed at 4 days, 8 weeks and 16 weeks. Increased levels of IGF-I were observed in the liver as soon as 4 days after vector administration. Control cirrhotic rats showed increased hepatic expression of pro-inflammatory and pro-fibrogenic factors including transforming growth factor beta (TGFβ), tumor necrosis factor-alpha (TNFα), connective tissue growth factor (CTGF), and vascular endothelial growth factor (VEGF) together with upregulation of α-smooth muscle actin (αSMA), a marker of HSC activation. In IGF-I-treated rats the levels of all these molecules were similar to those of healthy controls by week 8 post-therapy. Of note, the decline of TGFβ, CTGF, VEGF and αSMA expression was more rapid in AAVIGF-I treated animals reaching statistical significance by day 4 post-therapy. IGF-I-treated rats showed similar improvement of liver function tests in parallel with upregulation of hepatocyte nuclear factor 4α (HNF4α), a factor that promotes hepatocellular differentiation. A significant decrease of liver fibrosis, accompanied by upregulation of the hepatoprotective and anti-fibrogenic hepatocyte growth factor (HGF), occurred in all IGF-I-treated rats but complete reversal of liver cirrhosis took place only in AAVIGF-I group. Therefore, AAVIGF-I reverts liver cirrhosis in rats, a capability which deserves clinical testing.

Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease (IBD). Medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been proven to be effective in IBD. This study aimed to analyze (i) the natural history of patients with PSC with or without IBD and (ii) the long-term efficacy of biologics in patients with PSC and concomitant IBD or rheumatological disorders. This study included 92 consecutive PSC patients, 50 (54.3%) men and 42 (45.7%) women, with a mean age of 32.0±14.3 years at diagnosis and a mean follow-up duration of 103.8±86 months. Forty-nine (53.3%) patients had associated IBD (38 ulcerative colitis, 10 Crohn's disease, one indeterminate colitis). No significant differences were found between PSC patients with and without associated IBD in terms of liver transplantation, cancer, and death rates. Cholangiocarcinoma was only identified among patients with PSC alone, whereas other cancers (hepatocellular carcinoma, colorectal, and gallbladder cancer) were found only in the group with associated IBD. Five PSC patients were treated with biologic agents: three with adalimumab and one with infliximab for IBD or for rheumatoid arthritis, and one patient with rituximab for rheumatoid arthritis. Adalimumab decreased alkaline phosphatase in two of three patients after 6 and 12 months, infliximab reduced γ-glutamyltransferase after 6 and 12 months, but liver function tests tended to deteriorate thereafter. Cholangiography changes remained stable in all patients. Biologic agents may improve liver function tests in PSC patients, but may be associated with adverse events including deterioration of liver function.

Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.

Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

Evaluation Of Possible Antifibrotic Effect Of Cholecalciferol, Calci-Potriol, Aliskiren, Ramipril And Eprosartan On Carbon Tetrachloride Induced Liver Fibrosis In Albino Rats

the present study aims to evaluate the possible anti-fibrotic effect of calci-potriol, cholecalciferol, aliskiren, eprosartan and ramipril on carbon tetra-chloride (CCl4) induced liver fibrosis in rats. Methods: Fifty six Spague Dawely rats were randomly allocated into seven groups. All rats were ex-posed to induction of hepatic fibrosis by intraperitoneal (ip) injection of CCl4 twice/week for 8 successive weeks except control healthy group. The rats were treated with either calcipotriol (20 ug/Kg), Cholecalciferol (500 IU/kg), aliskiren (10mg/kg), eprosartan (60mg/kg) and ramipril (10mg/kg) simulta-neously with CCl4 treatment. Results: all the tested drugs have significant improvement in liver function tests (liver enzymes, bilirubin and albumin), oxidative stress markers (reduced glutathione, malondialdehyde and nitric oxide), transforming growth factor-b1 (TGF-b1) and fibrotic score. Only cal-cipotriol and cholecalciferol are significantly decrease renin gene expres-sion in liver and kidney tissues while cholecalciferol alone has significant in-crease in serum calcium and 25 hydroxy vitamin D [25(OH)D] levels. Conclusion: these results suggest that calcipotriol, cholecalciferol, aliskiren, eprosartan and ramipril have antifibrotic effect. Vitamin D receptor (VDR) agonists (Calcipotriol and cholecalciferol) inhibit renin gene expression and have better antifibrotic effect than renin angiotensin blockers (aliskiren, ep-rosartan and ramipril). Eprosartan has better antifibrotic effect than aliskiren and ramipri

Clinical Course Following Partial External Biliary Diversion for Progressive Familial Intrahepatic Cholestasis 1: A Report of Two Patients

AIM: To better understand the effect of partial external biliary diversion (PEBD) in patients with progressive familial intrahepatic cholestasis 1 (PFIC1). MATERIALS AND METHODS: We analyzed quantitative changes in the concentrations of individual bile acids in serum, urine, and biliary bile, and concomitant changes in symptoms such as pruritus, in 2 patients whose PFIC1 clinically evolved to resemble the course of benign recurrent intrahepatic cholestasis (BRIC) upon treatment with PEBD. RESULTS: Patient 1 showed good therapeutic effect after PEBD including improved liver function test results and decreased total bile acids in serum, as well as decreased pruritus. The cholic acid (CA)/chenodeoxycholic acid (CDCA) ratio in biliary bile also decreased. Patient 2, however, experienced little decrease in pruritus after PEBD, and showed no clear change in the CA/CDCA ratio. Nonetheless, this patient’s course did not rapidly worsen. CONCLUSION: In PFIC1, increased bile secretion and a decreased CA/CDCA ratio in biliary bile may be the most important responses after PEBD. Relief of pruritus is also an important sign of therapeutic effect. Moreover, progression of symptoms in PFIC1 sometimes can be delayed by PEBD, resulting in a relatively mild BRIC-like course, even when the CA/CDCA ratio and pruritus show little change. However, mechanisms underlying clinical benefits remain obscure.

Effect of canagliflozin on liver function tests in patients with type 2 diabetes

AimsTo report changes in liver function tests observed with canagliflozin, a sodium glucose co-transporter 2 inhibitor, across phase 3 studies in patients with type 2 diabetes, and to examine the relationship between changes in liver function tests and the weight loss and glycaemic improvements observed with canagliflozin. MethodsData were pooled from four 26-week, placebo-controlled studies of canagliflozin 100 and 300mg (n=2313) and two 52-week, active-controlled studies of canagliflozin 300mg versus sitagliptin 100mg (n=1488). Analysis of covariance was performed to determine the contribution of changes in body weight and HbA1c to the changes in liver function tests. ResultsReductions in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase, and increases in bilirubin were seen with canagliflozin 100 and 300mg versus placebo (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase [both doses]; P<0.001 for alkaline phosphatase and P=0.015 for bilirubin [canagliflozin 300mg only]) at week 26 and with canagliflozin 300mg versus sitagliptin 100mg (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and bilirubin, and P<0.01 for alkaline phosphatase) at week 52. Few patients met predefined limits of change criteria for liver function tests, and none met Hy's law criteria. In both populations, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase reductions were fully explained by HbA1c and body weight reductions. ConclusionsCanagliflozin provided improvements in liver function tests versus either placebo or sitagliptin treatments that were fully explained by the combined effects of HbA1c and body weight reductions with canagliflozin.

Autoimmune Hepatitis in Association With Sofosbuvir.

Sofosbuvir in combination with ribavirin was approved by the Food and Drug Administration as a treatment option for hepatitis C (HepC) in 2013. We describe a case of autoimmune hepatitis triggered in a patient on therapy with sofosbuvir and ribavirin. A 65-year-old woman with a medical history of diabetes mellitus, hypertension, and HepC (genotype 2) underwent pretreatment liver biopsy in May 2012, which demonstrated mild chronic active hepatitis with focal piece-meal necrosis and mild stage 1 periportal fibrosis with no increased iron deposition. No features of autoimmune hepatitis were seen on biopsy. The patient was administered 400 milligrams (mg) sofosbuvir and weight-based 1000 mg ribavirin for a planned duration of 12 weeks. Liver function tests (LFTs) initially improved on therapy; however, 3 weeks after the treatment initiation, the patient started complaining of weakness and fatigue. Repeat tests revealed elevated LFTs. Autoimmune titers were positive for antinuclear antibody, anti-smooth muscle antibody with elevated immunoglobulin (IgG), and serum gamma globulin levels. Repeat liver biopsy in June 2014 showed markedly distorted architecture secondary to formation of nodules completely enclosed by fibrous septa and areas of confluent necrosis with mild to moderate chronic inflammation consisting mainly of lymphocytes and plasma cells along with moderate to severe interface hepatitis. Ballooning degeneration of hepatocytes, with rosette formation possibly associated with regenerative activity was seen, consistent with superimposed autoimmune hepatitis. Based on laboratory and biopsy findings, diagnosis of drug-induced autoimmune hepatitis was made, and the treatment for HepC with sofosbuvir and ribavirin was discontinued. The patient was subsequently administered prednisolone with improvement in LFTs. We describe a patient with autoimmune hepatitis after initiation of sofosbuvir and ribavirin. To our knowledge, this complication has never been reported before in association with sofosbuvir. The most frequent adverse events noticed with this combination regimen have been headache, anemia, fatigue, and nausea.

Switching to anidulafungin from caspofungin in cancer patients in the setting of liver dysfunction is associated with improvement of liver function tests.

Anidulafungin does not undergo hepatic metabolism like the other echinocandins. Therefore, there is a perception that anidulafungin may be less hepatotoxic or less likely to exacerbate existing liver damage. This has not been substantiated in the literature. We retrospectively reviewed all cancer patients in whom anidulafungin treatment was immediately preceded by treatment with caspofungin and there existed clinical or laboratory evidence of hepatic damage or dysfunction at M. D. Anderson Cancer Center from January 2010 to December 2013. Sixty-one patients were included in the study. Most patients had haematological malignancies (58, 95%), and the patients were administered hepatotoxic agents such as chemotherapeutic agents (47, 77%) and other medications (38, 62%) simultaneously. There were significant decreases in AST and ALT (P < 0.029 and P < 0.0017, respectively) between two timepoints (switch from caspofungin to anidulafungin and end of anidulafungin therapy). The median changes in AST, ALT and total bilirubin during anidulafungin therapy were -43 IU/L, -25 IU/L and -0.15 mg/dL, respectively. Over 70% of patients had favourable changes in hepatic enzymes or function, and values were stable and decreased at the end of anidulafungin therapy. On average, the percentage of patients with laboratory results meeting common terminology criteria for adverse events (CTCAE) grade ≥2 at the time of switching to anidulafungin was decreased at the end of treatment. Median serum values and trajectory of hepatic enzymes and hepatotoxicity usually decreased after switching to anidulafungin treatment in patients with abnormal liver function tests. Anidulafungin could be useful in the management of cancer patients with hepatotoxicity occurring during caspofungin therapy.

The Protein-Sparing Modified Fast for Adolescents With Severe Obesity

Background. Severely obese youth respond poorly to current conventional lifestyle interventions when compared with their overweight and obese peers. The protein-sparing modified fast (PSMF) intervention is a reduced-calorie, low-carbohydrate, high-protein diet that is thought to improve weight loss. The objective of this study is to describe 2 inpatient cases and 1 outpatient case that used the PSMF for adolescents. Methods. Three patients followed a PSMF for approximately 12 to 52 weeks, initially consuming 20 to 40 grams of carbohydrate per day for the first 12 weeks. Two of these patients were admitted as inpatients for the first 2 to 4 weeks of the diet. Results. The PSMF led to rapid weight loss and a decrease in body mass index. For 2 patients, there was an improvement in liver function tests or liver disease following the PSMF diet. All the patients demonstrated an improvement in some abnormal laboratory indices, for example, liver function tests and hemoglobin A1c, but had a clinically insignificant increase in total cholesterol. No serious complications were observed. Conclusions. With proper planning and adequate resources, PSMF or low-carbohydrate diets are a viable option for the management of severe obesity in medically complex adolescents. However, practitioners will need to be conservative with its application in the pediatric population. Further research is needed to assess the long-term outcomes from a PSMF.

May Ursodeoxycholic Acid Significantly Improve Liver Function Tests among Patients with Hepatitis C?

In their relevant study, the authors demonstrated that ursodeoxycholic acid therapy significantly improvedliver function tests either when given alone or combined with silymarin. But, silymarin itself failed to improve liver function tests. We thank to the authors for their valuable contribution. However, there are some concerns that need to be explained in a detailed manner for a better understanding of the results presented in the manuscript. Key Words: Ursodeoxycholic acid, liver function, hepatitis C

Hepatocellular Autophagy in Anorexia Nervosa (AN)

Introduction: We report a rare entity of liver autophagy syndrome in a chronically starved patient recently started on oral feeding, since this can be a potentially fatal complication. Case Report: A 22-year-old female with AN was admitted from an inpatient psychiatry ward for failure to thrive with weight loss of 18 lbs over 2 months. She was started on a regular diet with close monitoring of electrolytes for re-feeding syndrome. On admission, the patient weighed 55 lbs with a height of 62 in and BMI of 10. She was found to have elevated liver function tests (see table). Her extensive work-up for abnormal liver function tests (LFTs) was unremarkable, and the patient was presumed to have hepatocellular autophagy. She was started on low protein and carbohydrate diet with frequent monitoring of her LFTs and electrolytes. Her diet was gradually increased with subsequent normalization of LFTs. Discussion: Autophagy results in the formation of autophagosomes, which fuse with lysosomes where degradation occurs. Autophagy is involved in cell homeostasis, and the best known role of autophagy is in its action during starvation. Macromolecules resulting from autophagy are presumably released from the vacuoles for reuse in the cytosol and are a source of continued biosynthesis. Autophagy also delays apoptosis in a cell during nutrient deprivation, and is a survival strategy under stress condition. However, recent studies have shown that autophagy can effectively kill a cell if the components are rapidly consumed as suspected in our patient. There are no guidelines in the management of acute liver injury in patients with anorexia nervosa. Improvement in LFTs has been reported with adequate nutritional support and close monitoring of electrolytes. Several authors recommend a low protein and carbohydrate diet with a theoretical benefit to prevent re-feeding steatosis. Anorexia nervosa with extremely poor nutritional status should be included in the differential diagnosis of acute liver injury. Our findings suggest that starvation-induced autophagy played a role in hepatocellular death resulting in acute liver injury.Table 1: Summary of Liver Function Tests

Can antiretroviral therapy modify the clinical course of HDV infection in HIV-positive patients?

Infection with hepatitis delta virus (HDV) affects approximately 6-14.5% of patients coinfected with HIV-1 and HBV, showing a more aggressive clinical course compared with an HIV-negative population. There is no universally approved treatment for chronic hepatitis D (CHD) in HIV-infected patients. Antiretroviral therapy (ART) containing tenofovir has been recently associated with HDV suppression. Our aim was to evaluate whether the outcome of CHD in HIV-infected patients can be favourably influenced by ART including reverse transcriptase inhibitors. The clinical course of four HBV/HDV/HIV-coinfected patients receiving ART were retrospectively examined. HDV RNA became undetectable in all patients after a variable period of ART along with the disappearance of hepatitis B surface antigen in two of them, and an increase in CD4(+) T-cell count. In all patients, virological changes were associated with improved liver function tests and clinical features. We suggest that ART regimens including drugs active against HBV could have beneficial effects on the clinical course of CHD in patients with HIV-1 by favouring immunological reconstitution.

Colic and gastric over-the-scope clip (Ovesco) for the treatment of a large duodenal perforation during endoscopic retrograde cholangiopancreatography.

Successful management of endoscopic retrograde cholangiopancreatography (ERCP)-related duodenal perforations, up to 20 mm, has been reported using several endoscopic devices [Von Renteln et al. 2010; Buffoli et al. 2012; Dogan et al. 2013; Donatelli et al. 2013; Meduri et al. 2014], however, surgery remains the standard of care management of larger defects [Wu et al. 2006; Lee et al. 2013]. Here we report, to the best of the authors’ knowledge, the first case of successful treatment of a large duodenal perforation (>20 mm) during ERCP, using several Ovesco clips. A 66-year-old white man was addressed for biliary drainage due to important cholestasis secondary to a liver metastatic lesion of an urothelial cancer treated by surgery and chemotherapy. During ERCP and while delivering the third plastic 10F stent (Figure 1) a movement of the endoscope provoked a large retroperitoneal duodenal perforation occupying 1/3 of the duodenal wall (Figure 2), opposite to the papilla at the early beginning of second duodenum. The size of perforation was important, mostly because the duodenal wall is thin and injury provoked a mucosal laceration with tearing of the wall. The decision to deliver a plastic stent instead of a metal one was taken given the poor prognosis of the patient, and namely because the stenosis was evaluated as ‘Bismuth IV’, and in the case of no improvement of liver function tests, a radiological percutaneous transhepatic approach would be compromised. Then the duodenoscope together with the partially delivered stent were immediately retrieved. A standard gastroscope loaded with an 11t Ovesco (OTSC®; Ovesco Endoscopy GmbH, Tubingen, Germany), under CO2 insufflation, was introduced but unfortunately the duodenal tear was too large, both in length and width, making it impossible to aspirate both edges of the tear in the cap or approach using a Twin Grasper®. A coloscope loaded with a 14t Ovesco was subsequently introduced and endoscopic suturing was started between the greater omentum and one edge of the duodenal tear (Figure 3). Since a closure defect persisted at the other end as shown after contrast-medium injection (Figure 4), the gastric Ovesco was delivered while aspirating the omentum incarcerated between the first colic clip and the free edge of the perforation, achieving full closure without contrast-medium extravasation (Figure 5). A nasogastric tube was left in place in soft aspiration. The patient was then transferred to the intensive care unit (ICU), for surveillance, where he remained for 7 days before being discharged. During his stay in the ICU, no fever was detected, the liver function tests were improved, and no further ERCP was needed to add the third stent. We only noticed a transient rise of the C-reactive protein, before its complete normalization, and CT scan as well as water-soluble contrast upper-studies performed on days 2 and 5 postoperatively were normal (Figure 6). Oral nutrition was started on day 6. At 1 month after endoscopy, the patient is fully asymptomatic. Figure 1. Hilar stenosis with 2 plastic stents in place. The guidewire in the left duct is about be placed, in order to deliver the third stent. Figure 2. Large duodenal defect. Figure 3. Colic clip Ovesco in place incarcerating greater omentum. Figure 4. Contrast-medium extravasation at the one end of the duodenal perforation despite colic Ovesco placement, given the large size of the defect. Figure 5. Watertight closure achieved using a ‘bridge technique’ using Ovesco on Ovesco. Figure 6. CT scan showing clips in place with no extravasation of contrast medium. In conclusion OTSC is a surgery-sparing device, and colic and gastric clips together can be a useful tool for the closure of large duodenal defects. However, the use of a colic Ovesco should be considered too, mainly because of its size, for upper gastrointestinal interventions in an expert’s hands.