The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy. METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries. RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%). CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.

Beyond genotype-4: Direct-acting antiviral agents in patients with chronic hepatitis C infection from the Eastern Province of Saudi Arabia.

Background and Aims: Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained virologic response (SVR) rate. However, the published data from the Eastern Province of Saudi Arabia are limited to small patient groups and specific DAAs used for patients with genotype-4.(GT-4). This study aimed to investigate the effectiveness and safety of DAAs for treating HCV infection in Saudi Arabia in a real-life setting. Methods: This retrospective study from January 2015 to December 2019 included all HCV-infected patients who received DAAs at a tertiary university hospital in Saudi Arabia. Baseline characteristics and laboratory data were collected from health records, including HCV RNA level, genotype, and presence of liver cirrhosis or steatosis. The primary outcome was undetectable HCV RNA at 12 weeks posttreatment (SVR12). Results were stratified based on different DAAs and HCV genotypes. Treatment-related adverse events were recorded. Statistical analyses were performed using SPSS version 25.0. Results: Of the 117 patients included, 43.2% had advanced fibrosis or cirrhosis, and the majority (90.6%) were treatment-naïve. The mean age was 50.1 ± 15.5 years, with 57.3% females. The most common genotype was GT-4 (44.4%), followed by GT-1 (40.2%). Most patients (64.3%) received sofosbuvir and daclatasvir ± ribavirin, while the remaining patients received various DAAs. Overall, 98.3% of the patients achieved SVR12. The therapy was well tolerated, with fatigue and headache being the most common side effects. Conclusions: Treatment with DAAs is highly effective across different genotypes and various DDA regimens in the real world for treating HCV infection in the Eastern Province of Saudi Arabia, contributing to improved patient outcomes and the overall goal of HCV elimination.

A novel candidate hepatitis C virus genotype 4 subtype identified by next generation sequencing full-genome characterization in a patient from Saudi Arabia.

Background and aim: Hepatitis C virus (HCV) infection is a major global public health concern, being a leading cause of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The virus is classified into 8 genotypes and 93 subtypes, each displaying distinct geographic distributions. Genotype 4 is the most predominant in the Middle East and Eastern Mediterranean and is associated with high rates of hepatitis C infection worldwide. This study used next-generation sequencing to fully characterize the HCV genome and identify a novel subtype within genotype 4 isolated from a 64-year-old Saudi man diagnosed with hepatitis C. Methods: We analyzed the complete genome of the 141-HCV isolate using whole-genome sequencing. Results: Our phylogenetic reconstructions, based on the entire genome of HCV-4 strains, revealed that the 141-HCV isolate formed a distinct group within the genotype 4 classification, providing valuable new insights into the variability of HCV. Conclusion: This discovery of a previously unclassified HCV subtype within genotype 4 sheds light on the ongoing evolution and diversity of the virus. Such knowledge has significant implications for diagnostic and therapeutic approaches, as different subtypes may exhibit varying drug sensitivities and resistance profiles.

Surgical Management of Intra-gastric Balloon Complications, Single-Center Experience, and Literature Review.

INTRODUCTION: In Saudi Arabia, the prevalence of obesity has multiplied in the last decades leading to a surge in bariatric surgery and other endoscopic modalities. The intra-gastric balloon (IGB) is the most used endoscopic modality. Surgical management for IGB complications is required for gastrointestinal perforation and/or obstruction. However, the literature seems to underestimate these complications. MATERIALS AND METHODS: A retrospective descriptive study was conducted in King Fahd University Hospital, Saudi Arabia, from Jan 2017 to Dec 2021, including all patients with complicated IGB who necessitated any surgical procedure. Exclusion criteria were patients with complicated IGBs that were only managed conservatively or endoscopically. RESULTS: A total of 326 patients were admitted with different complications after bariatric procedures. Of them, six patients were referred due to IGB complications that necessitated operative intervention. All patients were young females. Three patients had gastric wall perforation, and were managed by endoscopic removal of the IGBs followed by exploratory laparotomy. One patient had an intestinal obstruction on top of a migrated IGB that was surgically removed. One patient had failed endoscopic retrieval of IGB and required a laparoscopic gastrostomy. Another patient had an esophageal rupture that required left thoracotomy, pleural flap, and insertion of an esophageal stent. All cases were discharged and followed up with no related complications. CONCLUSION: IGB is an endoscopic alternative, within specific indications, for the management of obesity. However, surgical management may be necessary to manage its complications, including gastrointestinal perforation, IGB migration, and failure of endoscopic removal.

Insulin resistance induced by de novo pathway-generated C16-ceramide is associated with type 2 diabetes in an obese population.

BACKGROUND: Obesity and diabetes are two chronic metabolic diseases whose prevalence is increasing at an alarming rate globally. A close association between obesity, diabetes, and insulin resistance has been identified, and many studies have pinpointed obesity as a causal risk factor for insulin resistance. However, the mechanism underlying this association is not entirely understood. In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. METHODS: The samples comprised subcutaneous adipose tissues collected from three cohorts: lean non-diabetic (controls; n = 20), obese-non-diabetic (n = 66), and obese-diabetic (n = 32). Ceramide levels were quantified using LC-MS/MS and mRNA expression level for different enzymes were estimated using real-time PCR-based RNA expression analysis. RESULTS: C16-ceramide (P = 0.023), C16-dihydro-ceramide (P < 0.005), C18-dihydro-ceramide (P = 0.009) and C24-ceramide (P = 0.040) levels were significantly increased in the obese cohort compared to the control group. However, stratification of the obese group revealed a significant increase in the C16-ceramide levels (P = 0.027) and mRNA over expression of the serine palmitoyl transferases enzyme subunit SPT1 (P < 0.005) in the obese-diabetic cohort compared to the obese-non-diabetic cohort. CONCLUSIONS: The present study indicates that C16-ceramide plays a pivotal role in inducing insulin resistance. Overexpression of SPT1 in the obese-diabetic group and its positive correlation with C16-ceramide suggest that C16-ceramide was generated through the de novo pathway.

Gastrointestinal manifestations of COVID-19 in a single center in the Eastern Province of Saudi Arabia.

Background: Several gastrointestinal (GI) symptoms have been associated with novel coronavirus disease-2019 (COVID-19). Their prevalence and relation to the severity and hospital outcome of COVID-19 have not been well reported in the Middle East and Saudi Arabia. We aimed to examine the GI manifestations of COVID-19 and their association with the severity and hospital outcome of COVID-19 infection. Methods: We conducted a retrospective observational study of hospitalized COVID-19 patients who had a positive SARS-COV2 PCR test and were admitted at a university hospital in Saudi Arabia, from March to September 2020. The primary objective of the study was to describe the GI manifestations of COVID-19. The secondary objective was to investigate the association of GI manifestations with severity and outcome of COVID-19 infection. Results: We included 390 patients, of which 111 (28.5%) presented with GI manifestations. The most common presentation was diarrhea followed by nausea, vomiting, and abdominal pain. Patients without GI manifestations had a higher risk of severe-critical COVID-19 infection evident by the development of lung infiltration in more than 50% of lung fields within 24-48 h, acute respiratory distress syndrome, altered mental status, multiorgan failure, and cytokine storm syndrome (P < 0.05). These patients had a higher mortality rate compared to patients with GI manifestations (P = 0.01). A lower odds of death was seen among patients with GI symptoms (AOR 0.36; 95% CI, 0.158-0.82; P = 0.01). Conclusion: COVID-19 infection presents commonly with GI manifestations. Patients with GI manifestations have less severe COVID-19 disease and lower mortality rates.

Advancing the global public health agenda for NAFLD: a consensus statement.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients.

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M + M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up, whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

Concomitant hepatic tuberculosis and hepatocellular carcinoma: a case report and review of the literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that is strongly associated with chronic liver disease. Isolated hepatic tuberculosis is an uncommon type of tuberculosis. Concomitant occurrence of both conditions is extremely rare. CASE PRESENTATION: We report the case of a 47-year-old man who presented with fever and abdominal pain for 3 months prior to presentation. He reported a history of anorexia and significant weight loss. Abdominal examination revealed a tender, enlarged liver. Abdominal computed tomography (CT) demonstrated a solid heterogeneous hepatic mass with peripheral arterial enhancement, but no venous washout, conferring a radiological impression of suspected cholangiocarcinoma. However, a CT-guided biopsy of the lesion resulted in the diagnosis of concomitant HCC and isolated hepatic tuberculosis. CONCLUSION: A rapid increase in tumor size should draw attention to the possibility of a concomitant infectious process. Clinicians must have a high index of suspicion for tuberculosis, especially in patients from endemic areas, in order to initiate early and proper treatment.

Gastrointestinal stromal tumors. A clinicopathological study.

OBJECTIVES: To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data. METHODS: Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning. Results: The median age of patients was 54 years  (range; 17-81 years). Predominantly, we found more females were affected. The male to female ratio was 1:1.7. The most frequently affected organs were the stomach (63.8%) followed by small bowel (25%) and colorectal region (8.4%). Abdominal pain was the most frequent presentation in 33.3% of the patients then gastrointestinal (GI) bleeding in 30.5%. Most of the gastric GISTs were at early stages at presentation: stage 1 and II (60.8%), while in non-gastric GISTs, the tumor stage was advanced: stage III and IV (69.3%). The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%). CONCLUSION: Gastrointestinal stromal tumors in our study demonstrates a major similar feature as the published international data. However, minor differences do exist in terms of clinical features and immunohistochemistry.

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia.

BACKGROUND/AIMS: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. PATIENTS AND METHODS: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). RESULTS: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012). CONCLUSIONS: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.

Association of Uncoupling Protein 1 (UCP1) gene polymorphism with obesity: a case-control study.

BACKGROUND: Obesity is one of the main causes of morbidity and mortality worldwide. More than 120 genes have been shown to be associated with obesity related phenotypes. The aim of this study was to determine the effect of selected genetic polymorphisms in Uncoupling protein 1 (UCP1) and Niemann-Pick C1 (NPC1) genes in an obese population in Saudi Arabia. METHODS: The genotypes of rs1800592, rs10011540 and rs3811791 (UCP1 gene) and rs1805081 and rs1805082 (NPC1 gene) were determined in a total of 492 subjects using TaqMan chemistry by Real-time PCR. In addition, capillary sequencing assay was performed to identify two specific polymorphisms viz., rs45539933 (exon 2) and rs2270565 (exon 5) of UCP1 gene. RESULTS: A significant association of UCP1 polymorphisms rs1800592 [OR, 1.52 (1.10-2.08); p = 0.009] was observed in the obese cohort after adjusting with age, sex and type 2 diabetes. Further BMI based stratification revealed that this association was inconsistent with both moderate and extreme obese cohort. A significant association of UCP1 polymorphisms rs3811791 was observed only in the moderate-obese cohort [OR = 2.89 (1.33-6.25); p = 0.007] but not in the extreme-obese cohort indicating an overlying genetic complexity between moderate-obesity and extreme-obesity. The risk allele frequencies, which were higher in moderate-obese cohort, had abnormal HDL, LDL and triglyceride levels. CONCLUSION: The rs1800592 and rs3811791 of UCP1 gene are associated with obesity in general and in the moderate-obese group in particular. The associated UCP1 polymorphisms in the moderate-obese group may regulate the impaired energy metabolism which plays a significant role in the initial stages of obesity.

Analysis of the Impact of Common Polymorphisms of the FTO and MC4R Genes with the Risk of Severe Obesity in Saudi Arabian Population.

BACKGROUND: Obesity has reached epidemic proportions worldwide resulting in a serious public health problem. In Saudi Arabia, 28.7% of the population is obese due largely to the adoption of western dietary patterns over the last decade. The fat-mass and obesity associated (FTO) and melanocortin-4 receptor (MC4R) genes are ubiquitously expressed in the brain and pancreatic islets, and are the main link between the central nervous system and energy homeostasis based on food intake and energy expenditure. Genetic variants in the FTO and MC4R genes have been strongly associated with an increased obesity risk. AIM: To identify novel mutations in the MC4R gene and to perform correlation analyses of the known variants rs9939609 and rs1421085 in the FTO gene and rs17782313 near the MC4R gene in an obese Saudi population. MATERIALS AND METHODS: A total of 136 obese patients and 104 healthy controls from King Fahd Hospital, Al-Khobar, were genotyped for single-nucleotide polymorphisms within or near the FTO and MC4R genes using the TaqMan assay. Leptin levels were determined by enzyme-linked immunosorbent assay. Targeted sequencing of MC4R exon was done by Sanger sequencing method. RESULTS: The study included 58 obese males and 78 obese females with a mean age of 39.78 ± 12.77 years and a mean body mass index (BMI) of 42.65 ± 9.03 kg/m2. A significant increase in the levels of leptin and triglycerides was associated with an increase of BMI. Other factors such as lactate dehydrogenase, gamma-glutamyltransferase, and high-density lipoprotein were also significantly higher in the severely obese cohort. The FTO polymorphisms were associated with a significantly increased risk for obesity and in BMI-stratified cohort, rs9939609 (T/A: odds ratio [OR] = 1.73, p = 0.007) and rs1421085 (T/C: OR = 1.56, p = 0.03) showed even stronger association. Genotyping for the near MC4R polymorphism, rs17782313 revealed an association with moderately obese patients (T/C: OR = 1.73, p = 0.038). CONCLUSION: The studied FTO gene polymorphisms were found to be significantly associated with increased BMI and were highly significantly associated with severe obesity. These FTO gene polymorphisms combined with a high-fat diet appear to promote early-onset obesity in the Saudi population. FTO polymorphisms appear to be universally associated with the risk of obesity, and further investigation into this genetic locus may provide clues for potential therapeutic targets.

Validation of the postgraduate hospital educational environment measure at a Saudi university medical school.

OBJECTIVE: The English version of the postgraduate hospital educational environment measure (PHEEM) was evaluated to determine its psychometric properties, validity, and internal consistency. The instrument was used to measure the clinical learning environment in the hospital setting of a Saudi university medical school. METHODS: This cross-sectional study was performed in a Saudi medical school between June and August 2012. The postgraduate hospital educational environment measure was administered to interns (house officers) and residents rotating at a Saudi university hospital. Means and mean ranks were calculated. The effects of training stage (intern versus resident) and gender (male versus female) on the PHEEM scores were estimated. Construct validity was measured using exploratory factor analysis, and internal consistency was measured using Cronbach's alpha. RESULTS: In this study, 193 interns and residents responded to the PHEEM. The response rate was 100%. The internal consistency of the 40-item questionnaire was 0.936 (Cronbach`s alpha) with a maximum score of 160. The PHEEM mean score was 89.21 +/- 21.6. CONCLUSION: The PHEEM is a valid and highly reliable instrument that can be applied to measure the educational environment among interns and residents in hospital-based clerkships. The hospital training environment was positive, and the interns were more satisfied than the residents. Gender had no influence on the perceptions of the hospital`s educational environment.

Prediction of sustained virologic responses to combination therapy of pegylated interferon-α and ribavirin in patients with chronic hepatitis C infection.

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection is a major health problem worldwide. Genotype-4 is the most common genotype in Saudi Arabia. The response to treatment with pegylated interferon-α combined with ribavirin in chronic HCV infection varies. This study aimed at investigating the pre- and on-treatment predictors of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) infection. PATIENTS AND METHODS: Clinical data of 48 patients with CHC treated with standard HCV antiviral combination therapy, between January 2005 and December 2010, at a Saudi University hospital, were retrospectively reviewed for age, sex, body mass index, liver enzymes, HCV-RNA viral load, liver biopsy, and response to treatment. The primary end point was SVR defined as undetectable HCV-RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Univariable logistic regression was used to explore the association between the different variables and SVR. These independent predictors of SVR were then analyzed with multivariable logistic regression analysis. RESULTS: Of the 48 treated patients, 25 (52%) were females and 27 (56%) were Saudi. The mean age was 43 years (43 ± 10 years). Twenty-four (50%) had genotype-4, and 26 (54%) had liver biopsy. The overall SVR rate was 75% (36/48) and was 83.3% (20/24) among genotype-4 patients. Baseline factors associated with SVR identified by univariate logistic regression were genotype-4 and early viral response (EVR), defined as a drop of ≥2 log in serum HCV viral load after 12 weeks of initiation of combination therapy (P = 0.001). However, in stepwise regression analysis, the independent factor associated with the effect of antiviral therapy was genotype-4. When on-treatment variables were included, EVR (P = 0.003) and low baseline viral load (P = 0.048) were highly predictive of SVR. CONCLUSIONS: Of our HCV-treated patients, 75% had SVR. HCV genotype-4, EVR, and low baseline viral load were predictive of SVR.

Frequency of low bone mineral density in Saudi patients with inflammatory bowel disease.

BACKGROUND/AIMS: Metabolic bone disease is common in patients with inflammatory bowel disease (IBD). Our aim was to determine the frequency of bone loss among Saudi patients with IBD and possible contributing risk factors. SETTINGS AND DESIGN: We retrospectively reviewed Saudi patients with IBD, between 18 and 70 years of age, who had bone mass density (BMD) determined by dual-energy X-ray absorptiometry scanning at one of three hospitals in the Kingdom of Saudi Arabia from 2001 to 2008. PATIENTS AND METHODS: Case notes and BMDs results were carefully reviewed for demographic and clinical data. Low bone mass, osteopenia, and osteoporosis were defined according to the WHO guidelines. STATISTICAL ANALYSIS USED: Predictive factors for BMD were analyzed using group comparisons and stepwise regression analyses. RESULTS: Ninety-five patients were included; 46% had Crohn's disease (CD) and 54% had ulcerative colitis (UC). The average age was 30.9±11.6 years. Using T-scores, the frequency of osteopenia was 44.2%, and the frequency of osteoporosis was 30.5% at both lumbar spine and proximal femur. Only 25.3% of patients exhibited a BMD within the normal range. Our results revealed a positive correlation between the Z-score in both the lumbar spine and the proximal femur and body mass index (BMI) (P=0.042 and P=0.018, respectively). On regression analysis BMI, age, and calcium supplementation were found to be the most important independent predictors of BMD. CONCLUSIONS: Saudi patients with IBD are at an increased risk of low BMD and the frequency of decreased BMD in Saudi patients with CD and UC were similar. BMI and age were the most important independent predictors of low BMD.

Nonalcoholic fatty liver disease and type 2 diabetes mellitus: the hidden epidemic.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease worldwide. With obesity being a universally important risk factor, NAFLD is now receiving greater attention as a public health issue, and the burden of NAFLD is expected to increase in years to come. The prevalence of NAFLD among subjects with diabetes and with severe obesity is on the rise around the world, including in Saudi Arabia. Efforts in developing new strategies for its prevention, diagnosis and management are needed to alter the course of this disease. The purpose of this review is to enhance awareness about the close interrelationship between NAFLD and type 2 diabetes mellitus and recent diagnostic and treatment advances in the field.

Reversal of hepatic fibrosis: pathophysiological basis of antifibrotic therapies.

Chronic liver injuries of different etiologies eventually lead to fibrosis, a scarring process associated with increased and altered deposition of extracellular matrix in the liver. Progression of fibrosis has a major worldwide clinical impact due to the high number of patients affected by chronic liver disease which can lead to severe complications, expensive treatment, a possible need for liver transplantation, and death. Liver fibrogenesis is characterized by activation of hepatic stellate cells and other extracellular matrix producing cells. Liver fibrosis may regress following specific therapeutic interventions. Other than removing agents causing chronic liver damage, no antifibrotic drug is currently available in clinical practice. The extent of liver fibrosis is variable between individuals, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. Until recently it was believed that this process was irreversible. However, emerging experimental and clinical evidence is starting to show that even cirrhosis in its early stages is potentially reversible.

Glypican-3-Expressing Hepatocellular Carcinoma in a Non-Cirrhotic Patient with Nonalcoholic Steatohepatitis: Case Report and Literature Review.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Nonalcoholic steatohepatitis (NASH) is now considered as the major cause of cryptogenic cirrhosis, which can progress to HCC. Glypican-3 is a member of the Heparan Sulfate Proteoglycan (HSP) family that plays a role in cell growth, differentiation, and migration. Glypican-3 is significantly up-regulated in a majority of HCCs compared to normal and benign liver samples. Glypican-3 protein is detectable in around 40-53% of HCC patients whereas it is not detectable in the serum of healthy individuals. There are several reports of HCC arising in the setting of non-cirrhotic NASH. This report describes a case of HCC that expressed Glypican-3 and arose in a 47-year-old female with noncirrhotic NASH.