Clinical Characteristics of Autoimmune Hepatitis in a Middle Eastern Population: A Tertiary Care Center Experience.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause, and its manifestations appear to vary by race and ethnicity. The literature on AIH in the Middle East, including Jordan, is scarce; therefore, this study aimed to determine the clinical characteristics of AIH in an understudied population. This retrospective chart review study was conducted on AIH patients who presented to Jordan University Hospital over a seven-year period (2014-2020). Retrieved data included sociodemographics, liver function tests, autoimmune serologic markers, viral hepatitis serology, findings on liver biopsies, treatment regimens, post-therapy outcomes and treatment-related complications. The total number of AIH patients included in the study was 30, divided as follows: type 1 AIH (n = 17, 56.7%), type 2 AIH (n = 2, 6.7%), seronegative AIH (n = 9, 30.0%), and two patients who had AIH-primary biliary cirrhosis overlap syndrome (6.7%). The mean age at diagnosis was 44 years (standard deviation: 17 years), with a female predominance (n = 25, 83.3%). Acute presentation was seen among 18 patients (60.0%). Mild to moderate fibrosis (F1 and F2 on METAVIR scoring system) without cirrhosis was observed among patients who underwent liver biopsies (10/19, 52.6%). The majority of patients (73.3%) were initially treated with prednisone, with azathioprine combination in 16.7% of the patients. At 6 months post initial treatment, twenty patients (66.7%) achieved biochemical remission, four patients had incomplete response, two patients failed to improve (one died during the induction of remission period due to AIH-related complications), and four patients were lost to follow-up. This study provided an updated overview of AIH in Jordan. The results showed typical female predominance, and interestingly high rates of acute presentation and seronegative disease. Future longitudinal studies are recommended to address the nature and long-term prognosis of AIH in Jordan.

Prevalence of anxiety and depressive symptoms in ulcerative colitis patients in Jordan and its relationship to patient-reported disease activity.

Inflammatory bowel disease is associated with higher rates of anxiety and depression compared to the general population. We aimed to determine the prevalence of anxiety and depressive symptoms among patients with ulcerative colitis and correlation to disease activity. In this cross-sectional study, we collected data from 70 consecutive ulcerative colitis patients over one year at our inflammatory bowel disease outpatient clinic through an interview and a questionnaire containing patient demographics and disease characteristics. Anxiety and depressive symptoms were characterized using the Generalized Anxiety Disorder-7 questionnaire and Patient Health Questionnaire-9, respectively, with ulcerative colitis disease severity assessed by the Partial Mayo scoring system. The majority of our patients were females (68.6%) and the mean age was 39.3 years. Rates of anxiety and depressive symptoms among ulcerative colitis patients were 65.7% and 58.6%, respectively. Depressive symptoms were significantly associated with patient-reported disease activity (r = 0.361; p = 0.010). Significant percentages of ulcerative colitis patients were appreciated to have anxiety and depressive symptoms, and there was a correlation between patient-reported disease activity and depressive symptoms. At this high rate of prevalence, it is justified to screen patients for the presence of psychiatric comorbidities.

The probiotic supplementation role in improving the immune system among people with ulcerative colitis: a narrative review.

OBJECTIVES: The purpose of this paper is to summarize the current evidence on probiotics' uses as an adjuvant for ulcerative colitis (UC) and provide an understanding of the effect of probiotics supplement on the immune system and inflammatory responses among UC patients and subsequent therapeutic benefits. CONTENT: A narrative review of all the relevant published papers known to the author was conducted. SUMMARY: UC is a chronic inflammatory bowel disease (IBD) that results in inflammation and ulceration of the colon and rectum. The primary symptoms of active disease are diarrhea, abdominal pain, and rectal bleeding. About 70% of the human immune system (mucosal-associated lymphoid tissue) originates in the intestine. Probiotics are live microorganisms that help in stabilizing the gut microbiota (nonimmunologic gut defense), restores normal flora, and enhance the humoral immune system. Probiotics especially Bifidobacterium, Saccharomyces boulardii, and lactic acid-producing bacteria have been used as an adjunct therapy for treating UC to ameliorate disease-related symptoms and reduce relapse rate. Probiotics, in general, modulate the immune system through their ability to enhance the mucosal barrier function, or through their interaction with the local immune system to enhance regulatory T cell responses, decrease the pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin 1 beta and increase anti-inflammatory factor interleukin 10. OUTLOOK: More studies are needed to explore the properties of the various probiotic bacterial strains, their different uses, as well as the dosage of probiotics and duration for treating different disorders. Further clinical investigations on mechanisms of action and how probiotics modulate the immune system may lead to further advances in managing IBD.

The probiotic supplementation role in improving the immune system among people with ulcerative colitis: a narrative review.

OBJECTIVES: The purpose of this paper is to summarize the current evidence on probiotics' uses as an adjuvant for ulcerative colitis (UC) and provide an understanding of the effect of probiotics supplement on the immune system and inflammatory responses among UC patients and subsequent therapeutic benefits. CONTENT: A narrative review of all the relevant published papers known to the author was conducted. SUMMARY: UC is a chronic inflammatory bowel disease (IBD) that results in inflammation and ulceration of the colon and rectum. The primary symptoms of active disease are diarrhea, abdominal pain, and rectal bleeding. About 70% of the human immune system (mucosal-associated lymphoid tissue) originates in the intestine. Probiotics are live microorganisms that help in stabilizing the gut microbiota (nonimmunologic gut defense), restores normal flora, and enhance the humoral immune system. Probiotics especially Bifidobacterium, Saccharomyces boulardii, and lactic acid-producing bacteria have been used as an adjunct therapy for treating UC to ameliorate disease-related symptoms and reduce relapse rate. Probiotics, in general, modulate the immune system through their ability to enhance the mucosal barrier function, or through their interaction with the local immune system to enhance regulatory T cell responses, decrease the pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin 1 beta and increase anti-inflammatory factor interleukin 10. OUTLOOK: More studies are needed to explore the properties of the various probiotic bacterial strains, their different uses, as well as the dosage of probiotics and duration for treating different disorders. Further clinical investigations on mechanisms of action and how probiotics modulate the immune system may lead to further advances in managing IBD.

Primary Intestinal Lymphangiectasia Causing Intussusception and Small Bowel Obstruction.

Abdominal lymphangiectasia is a rare disease manifestation with a variety of anatomic locations and clinical presentations. The gastrointestinal tract may be affected, and lymphangiectasia originating in the wall of the intestine has rarely been described. We present a case of primary small bowel lymphangiectasia causing intussusception in a 30-year-old woman who presented with emesis and gastrointestinal bleeding. This case emphasizes the clinical presentation, diagnosis, and management in adults with abdominal lymphangiectasia. We highlight the importance of a high clinical suspicion for lymphangiectasia in an adult with acute abdomen to avoid catastrophic morbidity.

Intrahepatic Cholangiocarcinoma Masquerading as Acute Fatty Liver of Pregnancy: A Case Report and Review of the Literature.

Cholangiocarcinoma (CCA) is an uncommon cancer and accounts only for 3% of all gastrointestinal malignancies. In this report, we present a case of an intrahepatic cholangiocarcinoma masquerading as acute fatty liver of pregnancy (AFLP). A 38-year-old female who is 36-week pregnant presented with a 1-week history of headache, nausea, vomiting, and right upper abdominal pain, along with hepatomegaly. Laboratory investigations were remarkable for mild leukocytosis, hyperbilirubinemia, proteinuria, and elevated transaminases and prothrombin time. Ultrasound of the liver revealed hepatomegaly, fatty infiltration, and a right hepatic lobe mass. Based on the overall picture, AFLP was suspected, and the patient underwent delivery by Cesarean section. However, bilirubin and liver enzyme levels gradually increased after delivery. MRI revealed a large dominant hepatic mass along with multiple satellite lesions in both lobes. Biopsy revealed the presence of intrahepatic CCA. CCA presenting during pregnancy is extremely rare with only 9 other cases reported in the literature. Therefore, the signs and symptoms can be easily confused with other more common disorders that occur during pregnancy.

Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic steatohepatitis (NASH), the most severe form of nonalcoholic fatty liver disease (NAFLD), is associated with inflammation and increased oxidative stress. The neutrophil/lymphocyte ratio (N/L) integrates information on the inflammatory milieu and physiological stress. AIMS: The aim of this study was to determine the utility of N/L ratio to predict the presence of NASH in patients with NAFLD. METHODS: Our cohort consisted of 101 consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were divided into two groups: NASH group (n = 50) and not NASH group (n = 51). The stage of fibrosis was measured using a 4-point scale. The total white cell count, neutrophil and lymphocyte counts were recorded, and the N/L ratio was calculated. RESULTS: The mean age was 49.5 (± 10.8) years and the mean BMI was 31.4 (± 4.9) kg/m(2) . Patients with NASH had a higher N/L ratio compared with patients with not NASH [2.5 (1.9-3.3) and 1.6 (1.2-2.0), respectively, P < 0.001]. The N/L ratio correlated with the NAFLD activity score and its individual components (steatosis, inflammation and ballooning P < 0.001). Patients with advanced fibrosis (F3-4) had an elevated N/L ratio [2.9 (2.0-3.9)] compared with patients with fibrosis stage 1-2 [1.8 (1.2-2.2)], P < 0.001. For each one-unit increase in N/L ratio, the likelihood of having NASH increased by 70% and the likelihood of having fibrosis increased by 50%. CONCLUSION: The N/L ratio is higher in patients with NASH and advanced fibrosis. This ratio can be used as a novel noninvasive marker to predict advanced disease.

An apoptosis panel for nonalcoholic steatohepatitis diagnosis.

BACKGROUND & AIMS: The extrinsic death receptor-mediated pathway of apoptosis is involved in nonalcoholic steatohepatitis (NASH) development. Our aims were to create and validate a noninvasive prediction model for NASH diagnosis based on specific circulating markers of apoptosis. METHODS: Our initial cohort consisted of 95 consecutive patients undergoing a liver biopsy for clinically suspected NASH. Blood was obtained from each patient at the time of liver biopsy. Plasma caspase 3 generated cytokeratin-18 fragments (CK-18), soluble Fas (sFas), and soluble Fas ligand (sFasL) were measured. Histology was assessed by an experienced hepatopathologist. The validation cohort consisted of 82 consecutive patients that underwent liver biopsy at the time of bariatric surgery. RESULTS: Patients with NASH had significantly higher levels of CK-18 and sFas than patients in the "not NASH" group [median (25th, 75th percentile): 508 (280, 846) U/L versus 176 (131, 224) U/L (p<0.001), and 11.8 (7.8, 12.5) ng/ml versus 5.9 (4.8, 8.3) ng/ml (p<0.001), respectively]. A significant positive correlation was revealed between the apoptosis markers and liver histopathology independent of other metabolic factors. A prediction model was generated including CK-18 fragments and sFas levels that showed an AUC of 0.93 and 0.79 in the initial and validation cohorts, respectively. A cutoff value using this model predicted NASH with a sensitivity and specificity of 88% and 89%, respectively. CONCLUSIONS: Quantification of circulating levels of two apoptotic markers accurately predicts the presence of NASH, supporting the potential usefulness of these markers in clinical practice for noninvasive diagnosis of NASH.

Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the pathways that contribute to oxidative damage in vivo are poorly understood. Our aims were to define the circulating profile of lipid oxidation products in NAFLD patients, the source of these products, and assess whether their circulating levels reflect histological changes in the liver. The levels of multiple structurally specific oxidized fatty acids, including individual hydroxy-eicosatetraenoic acids (HETE), hydroxy-octadecadenoic acids (HODE), and oxo-octadecadenoic acids (oxoODE), were measured by mass spectrometry in plasma at time of liver biopsy in an initial cohort of 73 and a validation cohort of 49 consecutive patients. Of the markers monitored, 9- and 13-HODEs and 9- and 13-oxoODEs, products of free radical-mediated oxidation of linoleic acid (LA), were significantly elevated in patients with nonalcoholic steatohepatitis (NASH), compared with patients with steatosis. A strong correlation was revealed between these oxidation products and liver histopathology (inflammation, fibrosis, and steatosis). Further analyses of HODEs showed equivalent R and S chiral distribution. A risk score for NASH (oxNASH) was developed in the initial clinical cohort and shown to have high diagnostic accuracy for NASH versus steatosis in the independent validation cohort. Subjects with elevated oxNASH levels (top tertile) were 9.7-fold (P < 0.0001) more likely to have NASH than those with low levels (bottom tertile). Collectively, these findings support a key role for free radical-mediated linoleic acid oxidation in human NASH and define a risk score, oxNASH, for noninvasive detection of the presence of NASH.

The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is a well-recognized cause of cirrhosis and has been increasingly associated with the development of hepatocellular carcinoma (HCC). The aims of this study were to (1) estimate the incidence of HCC in patients with NASH-related cirrhosis, (2) compare incidence in NASH-related cirrhosis with hepatitis C virus (HCV)-related cirrhosis, and (3) identify risk factors of HCC in patients with NASH-related cirrhosis compared with HCV-related cirrhosis. Adult patients with cirrhosis secondary to chronic HCV (n = 315) or NASH (n = 195) were evaluated at our hepatobiliary clinic between 2003 and 2007. To assess for HCC development, all patients were monitored using serial abdominal computed tomography and serum alpha-fetoprotein every 6 months. Kaplan-Meier analysis was performed to estimate the cumulative incidence of HCC. Descriptive statistics were computed for all factors. Univariate and multivariate Cox regression analysis were used to assess associations between HCC and factors of interest. The median follow-up was 3.2 years (25th percentile [P25], 75th percentile [P75]: 1.7, 5.7) during which 25/195 (12.8%) of NASH-cirrhotic and 64/315 (20.3 %) of HCV-cirrhotic patients developed HCC (P = 0.03). Yearly cumulative incidence of HCC was found to be 2.6% in patients with NASH-cirrhosis, compared with 4.0% in patients with HCV cirrhosis (P = 0.09). Multivariate regression analysis revealed that older age (P = 0.006) and alcohol consumption (P = 0.002) were independent variables associated with development of HCC in patients with NASH-cirrhosis. Compared with nondrinkers, patients who reported any regular alcohol consumption were at greater risk for HCC development (hazard ratio: 3.6; P25, P75: 1.5, 8.3). CONCLUSION: Patients with NASH cirrhosis have a greatly increased risk of liver cancer. Alcohol consumption, a modifiable risk factor, appears to be the most significant factor associated with risk of HCC development in our study population.

Complete subtalar release for older children who had recurrent clubfoot deformity.

BACKGROUND: Neglected idiopathic clubfoot deformities, and severe recurrent deformity after previous surgery presents technical difficulties for correction and challenges for surgeons to achieve primary skin closure. METHODS: Between 2000 and 2006, 18 children (30 feet), had complete subtalar release (CSTR) for failed previous surgery in 28 feet and severe neglected congenital talipes equinovarus (CTEV) in 2 feet followed by cross leg fasciocutaneous flaps for reconstruction of residual defect at the ankle and foot after full correction of the deformity. Mean patients followed up were 4.5 years (average 2-8 years). 23 feet were classified as Dimeglio III and 7 feet as Dimeglio IV. RESULTS: All cases achieved a plantigrade foot, better walking ability (p<0.03), and parental satisfaction with the result (p<0.001). Ankle joint doriflexion increased from mean (-21.33 degrees ) preoperatively to (12.5 degrees ) postoperatively. All cases showed postoperative improvement in their radiographic findings. The mean preoperative talocalcaneal angle increased from (15.7 degrees to 30.03 degrees ). The talo-first metararsal angle improved from a preoperative mean of -16 degrees mean of 5.53 degrees postoperatively. At the final follow-up cosmetically acceptable plantigrade foot was achieved in all feet. Four legs (14.28%) developed hypertrophic scars at the donar flap site. One patient developed 1.5cm marginal necrosis of the flap, which did heal after debridement by secondary intention. None of the feet had recurrence at the final follow up. Despite the enormous improvement clinically and radiologically, their was no statistical significant difference between preoperative and postoperative radiological angles (p<0.069). The number of previous surgical interventions had no influence on the outcome. All the previously treated feet had inadequate release of important tethered soft tissue. CONCLUSION: This is indicative of the enormous value of complete subtalar release combined with cross leg fasciocutaneous flap without the need for bony intervention in previously operated failed feet or neglected deformities.

The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It encompasses a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Growing evidence links NAFLD to cardiovascular (CV) disease; however, the association between the histologic severity of NAFLD and CV risk remains poorly understood. AIM: To assess the relationship between severity of liver injury and CV risk markers in a large, well-characterized group of patients with biopsy-proven NAFLD. METHODS: Our cohort consisted of 83 consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were subsequently divided into three groups: normal biopsy (n=11) simple steatosis (n=36), and NASH (n=36). CV risk markers included: triglyceride/high-density lipoprotein (HDL), total cholesterol/HDL, and low-density lipoprotein/HDL ratios. RESULTS: All lipid ratios were found to be significantly associated with NAFLD (p<0.05) after adjusting for age and gender. More importantly, there was a stepwise, statistically significant increase in lipid ratios from patients with normal biopsies to patients with simple steatosis to those with NASH (p<0.05). A positive correlation was found between the lipid ratios and NAFLD activity score (NAS) as well as the individual histological features of the NAS (steatosis, inflammation, and ballooning) with the strongest correlation being with NAS (rho (95% CI) 0.41 (0.21, 0.62), p<0.001). CONCLUSION: In patients with NAFLD, the histologic severity of liver injury and inflammation is strongly associated with an increased CV risk and an atherogenic lipid profile.

Recognizing and treating cutaneous signs of liver disease.

Cutaneous changes may be the first clue that a patient has liver disease. Recognizing these signs is crucial to diagnosing liver conditions early. Here we describe the spectrum of skin manifestations that may be found in various liver diseases.

Hepatitis B: a strategy for evaluation and management.

In hepatitis B virus (HBV) infection, a single approach to treatment cannot be applied to all patients. Acute, adult-acquired HBV infection rarely requires treatment, whereas treatment for chronic infection should be based on the patient's clinical situation and test results. The ideal agent for treating hepatitis B does not exist, and trade-offs are the essence of agent selection. In last month's Journal (Cleve Clin J Med 2008; 75:881-889), we outlined the natural history and diagnosis of chronic HBV infection; in this article we outline its management.

Hepatitis B virus infection: understanding its epidemiology, course, and diagnosis.

Although hepatitis B virus (HBV) infection is not as common in the United States as in some countries, 5000 Americans die from it every year. This number can be significantly decreased with proper screening and by vaccinating people at risk. Internists should be aware of the natural history of HBV infection, a vital prerequisite to correctly assessing disease severity and subsequently determining the need for antiviral therapy.