Predictors Of Fibrosis Research Articles

The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view.

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.

Delays in definitive endoscopic resection of previously manipulated colorectal polyps as a risk factor for inferior resection outcomes

Manipulation of colorectal polyps by biopsy, incomplete resection, or tattoo placement under the lesion has been shown to cause submucosal fibrosis and associated inferior outcomes. The effect of delays between index manipulation and definitive resection on the incidence of fibrosis is unknown. Patients undergoing EMR of previously manipulated colorectal polyps≥10mm from 2016 to 2021 at a tertiary referral center were included. Time from index manipulation to definitive resection and the presence of fibrosis were noted. The effects of fibrosis on EMR outcomes were assessed. Among 221 previously manipulated lesions (180 biopsy, 23 incomplete/failed resection, 1 tattoo under lesion, 17 multiple types of manipulation), 51 (23%) demonstrated fibrosis. Fibrotic lesions were found to have been resected significantly later than nonfibrotic lesions (76 vs 61 days; P= .014). In a multivariate analysis controlling for other predictors of fibrosis, each 2-week delay was associated with a 14% increase in the odds of fibrosis. Fibrotic lesions had inferior outcomes with a lower en-bloc resection rate (8% vs 24%; P= .014) and longer procedure time (71 vs 52 minutes; P< .001). Adverse event and recurrence rates were similar between groups. Delays in definitive resection of previously manipulated polyps are associated with an increased incidence of fibrosis with time and associated inferior outcomes. Manipulation should be discouraged, and if it occurs, prompt referral and scheduling for definitive resection should be prioritized.

ALBI and APRI score as prognostic factors for predicting the FABIB complications after liver resection in metastatic colorectal cancer.

e15577 Background: Previous studies and this study demonstrate that liver resection, even with subsequent extrahepatic relapse, may be associated with long-term survival, are very encouraging for future studies of the effectiveness of liver cytoreduction in conditions of minimal extrahepatic disease. These data also contribute to selective cytoreduction in extrahepatic sites. If it is necessary to achieve an oncological result (maximally extended liver resection), sometimes the surgical result suffers in the form of postoperative complications. The most serious complication of liver resection due to colorectal cancer metastases is postoperative liver failure, characterized by high levels of INR and bilirubin by day 5 after surgery. Methods: To classify the most frequent postoperative complications, the FABIB system has been developed, which includes Failure, Ascites, Bile leakage, Infection, Bleeding. We tried to evaluate the possibilities of using the ALBI and APRI indicators as one of the factors that must be taken into account when predicting the development of complications from the FABIB group. ALBI score is used in predicting the development of liver failure in patients with hepatocellular cancer. APRI score is a predictor of fibrosis and cirrhosis in patients suffering from hepatitis. Results: We have analyzed the results of liver resections in 174 patients with metastatic liver damage in colorectal cancer. Among them 57% are women, 43% are men. Metastatic lesion of the right lobe – 38 (21.8%), the left lobe – 78 (44.8%), right and left lobes – 58 (33.4%). Right–sided tumors - 25% - 43 patients, left–sided tumors - 75% - 131 patients. According to the FABIB classification, liver insufficiency was observed in 25 patients (14%), ascites in 4 patients (2.3%), bile leakage in 8 (4.6%), infectious complications in 9 (5%), bleeding in 15 patients (8%). A single-factor analysis of the variance of ALBI and APRI indicators on the day of surgery, the day after surgery and on the 5th day after surgery did not show a statistically significant difference in the groups with all FABIB complications and without FABIB complications. However, statistical analysis separately in each subgroup of complications revealed a statistically significant difference in ALBI and APRI in the groups with and without postoperative liver failure, as well as a statistically significant difference in the groups with and without bleeding. Conclusions: Thus, it can be concluded that ALBI score and APRI score can be used in the early postoperative period to predict the development of postoperative liver failure and hemorrhagic complications not only in patients with hepatocellular cancer or cirrhosis, but also in patients with colorectal cancer with liver metastases. It could be useful in patients who have undergone several lines of chemotherapy before liver resection or with a large tumor lesion of the liver.

Soluble CD163 is a predictor of fibrosis and hepatocellular carcinoma development in nonalcoholic steatohepatitis

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. The serum level of soluble CD163 (sCD163), a macrophage activation marker, is associated with liver tissue changes; however, its prognostic value is unknown. Here, we determined the utility of sCD163 as a marker for hepatocellular carcinoma (HCC) and prognostic marker for NAFLD.MethodsThis retrospective study obtained data regarding serum sCD163 levels, liver histology, and background factors associated with NAFLD in 287 patients (men/women, 140/147; average age, 53 ± 14 years) with NAFLD who underwent liver biopsy. Repeated liver biopsies of 287 patients with NAFLD (5.0 ± 2.7 years) were compared regarding serum sCD163 levels and liver tissue changes (stage, grade, steatosis, and NAFLD activity score).ResultsSerum sCD163 levels increased with the progression of liver fibrosis and inflammation (both P < 0.05) and were particularly helpful in distinguishing cases of Grade 4 fibrosis (P < 0.001). Levels of sCD163 significantly decreased in patients with NAFLD exhibiting alleviated fibrosis and inflammation (P < 0.05). We could also predict the development of HCC and associated mortality based on serum sCD163 levels at the time of NAFLD diagnosis. Serum sCD163 levels were higher in patients with HCC than in patients without HCC (1074 ± 379 ng/ml vs. 669 ± 261 ng/ml; P < 0.0001), and the same trend was observed for mortality.ConclusionsThe serum sCD163 level reflects the progression of fibrosis and inflammation in liver tissues, showing much promise as a noninvasive biomarker for nonalcoholic steatohepatitis and NAFLD as well as a possible predictor of HCC development and patient prognosis.

Cytokeratin 18 can help predict liver fibrosis in HCV infected patients with type 2 diabetes mellitus

BackgroundTo investigate the predictive values of cytokeratin 18 for liver fibrosis in hepatitis C virus (HCV) infected patients with type 2 diabetes mellitus (T2DM).Methods252 HCV-infected patients with T2DM between January 2012 and August 2017 were retrospectively reviewed. Pearson/spearman correlation analysis was used to detect the correlation in the entire cohort. Multivariate linear regression was used to identify independent predictors and logistic regression was for establishing models. Combination models that incorporated CK18 and other methods (i.e. transient elastography, aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4)] were developed in a training cohort of 132 patients. Performance of models was evaluated through discrimination ability and clinical benefits. An internal validation was conducted in 120 consecutive patients.ResultsCK18 was found significantly associated with fibrosis scores (r = 0.452, P < .001). CK18 and albumin were confirmed as independent predictors for fibrosis. For predicting significant fibrosis in the validation cohort, the observed AUC values of APRI + CK18 (AUC 0.83) and FIB-4 + CK18 (AUC 0.84) were higher than those of APRI (AUC 0.61) and FIB-4 (AUC 0.65). For predicting advanced fibrosis and cirrhosis, the AUC values of FIB-4 + CK18 (AUC 0.74 and 0.77, respectively) were significantly higher than those of FIB-4 (AUC 0.61 of both). Decision curve analysis confirmed the more clinical benefits can be provided by being combined with CK18.ConclusionsCK18 is an independent predictor of liver fibrosis for HCV-infected patients with T2DM. Noninvasive methods incorporate CK18 and other biomarker indices can have better performance for diagnosing fibrosis and help clinical decision-making.

Portal Venous Pulsatility Index as a predictor of fibrosis in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a growing public health issue. Non-invasive methods to assess the fibrosis stage are limited, and biopsy remains the gold standard. The objective of our study was to assess whether the portal venous pulsatility index (VPI) can be used as a predictor of high-risk NAFLD at a tertiary referral centre for liver transplantation. We retrospectively reviewed patients with biopsy-proved NAFLD who had undergone a liver ultrasound scan within 1 year of biopsy at our centre from 2011 to 2019. We did not find a significant correlation between the VPI and the NAFLD risk category or correlation between the VPI and degree of steatosis (P > 0.05 for both). Since VPI can be easily obtained on routine liver ultrasound and since other studies do report a positive association with significant fibrosis, more studies are needed before it can be recommended or not in risk-stratifying NAFLD patients into high- vs. low-risk NAFLD.

Non-obese non-alcoholic fatty liver disease (NAFLD) in Asia: an international registry study

BackgroundA significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients. Methods1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients. FindingsOne-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01–2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99–3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p < 0.001) when classifying patients with F2–4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease. ConclusionA substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

A Model Incorporating Serum Alkaline Phosphatase for Prediction of Liver Fibrosis in Adults with Obesity and Nonalcoholic Fatty Liver Disease.

We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients’ data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03; 95% Confidence interval (CI), 1.01–1.05), alanine aminotransferase (OR 1.02; 95% CI, 1.01–1.03), HbA1c (OR 1.58; 95% CI, 1.20–2.09), and body mass index (OR 1.06; 95% CI, 1.00–1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease.

A Multi-Center Study Exploring the Association of Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease in Cuban Patients

Aim: There is a paucity of data on Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Syndrome (MetS) among native Cubans. We aimed to assess the prevalence of MetS in Cubans with NAFLD and the outcomes and predictors for advanced fibrosis. Methods: A multicenter (outpatient clinics of nine hospitals in seven Cuban provinces) cross-sectional study of adults with NAFLD between September 2018 and May 2019. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP: ATPIII) criteria. Advanced fibrosis was defined using AST to Platelet Ratio Index (APRI) ≥1 and Fibrosis-4 score (FIB-4) ≥2.67. Results: 819 patients enrolled, 563 (68.7%) had MetS; mean age 54.9 years, 60.3% female, 65.8% white, 95.1% from urban residency, mean BMI 30.7 kg/m². Fibrosis was present in 114 (13.9%); 94 (82.5%) had APRI ≥1; 77 (67.5%) had FIB-4 ≥ 2.67; 57 (50%) both scores were elevated. MetS group had significantly more fibrosis than no MetS, [17% vs. 7% (p=0.0001)]. Patients with fibrosis were older (57.7 vs. 54.5, P=0.0015), of Mestizos ethnicity (36.8% vs. 16.9%, P&lt;0.0001), and from rural residency (17.5% vs. 2.8%, P&lt;0.0001). MetS was independently associated with fibrosis: Odds Ratio (OR) = 2.05 (95% CI 1.10-3.81) (p=0.024), but, rural residency was the strongest fibrosis predictor [OR: 5.30 (95% CI 2.45-11.47, (P&lt;0.0001)]. Other fibrosis predictors were male gender, sedentary life-style, NAFLD family history, and lower estimated glomerular filtration rate (p&lt;0.05). Risk of fibrosis was not associated with age, ethnicity, or smoking (all p&gt;0.05). Conclusion: Cuban NAFLD patients with MetS have substantial clinical impairment and a higher risk for fibrosis.

CT colonography followed by elective surgery in patients with acute diverticulitis: a radiological-pathological correlation study

PurposeTo perform a radiologic-pathologic correlation analysis of sigmoid colon in patients undergoing pre-operative CT Colonography (CTC) after an episode of acute diverticulitis (AD).MethodsFifty-nine consecutive patients (31/28 M/F; 58 ± 13 years) underwent CTC 55 ± 18 days after AD, 8 ± 4 weeks before surgery. Thirty-seven patients (63%) underwent conventional abdominal CT at time of AD. An experienced blinded radiologist retrospectively analyzed all images: disease severity was graded according to the Ambrosetti classification on conventional CT and according to the diverticular disease severity score (DDSS) on CTC. A GI pathologist performed a dedicated analysis, evaluating the presence of acute and chronic inflammation, and fibrosis, using 0–3 point scale for each variable.ResultsOf 59 patients, 41 (69%) had at least one previous AD episode; twenty-six patients (44%) had a complicated AD. DDSS was mild-moderate in 34/59 (58%), and severe in 25/59 (42%). All patients had chronic inflammation, while 90% had low-to-severe fibrosis. Patients with moderate/severe fibrosis were older than those with no/mild fibrosis (61 ± 13 versus 54 ± 13). We found a significant correlation between DDSS and chronic inflammation (p = 0.004), as well as DDSS and fibrosis (p = 0.005). Furthermore, fibrosis was correlated with complicated acute diverticulitis (p = 0.0.27), and with age (p = 0.067). At multivariate analysis, complicated diverticulitis was the best predictor of fibrosis (odds ratio 4.4). Patient age and DDSS were other independent predictors.ConclusionDDSS-based assessment on preoperative CTC was a good predictor of chronic colonic inflammation and fibrosis. In addition, the presence of complicated diverticulitis on CT during the acute episode was most predictive of fibrosis.

Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD)

Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment.Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD.Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression.Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5 ± 14.0, BMI 30.4 ± 5.9 kg/m2). Fibrosis stage F0/F1/F2/F3/F4 was observed in N = 7/47/7/17/9, an NAS ≥4 in N = 27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3–4.4, p = .005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2–4.4, p = .012) were significant predictors for fibrosis ≥ F2. Predictive factors for NASH were not identified.Conclusion: The biopsy rate in NAFLD patients is low and fibrosis ≥ F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.

Association between PNPLA3[G]/I148M variant, steatosis and fibrosis stage in hepatitis C virus - genetic matters.

There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression.

CORRELATION OF AA INDEX WITH DEGREE OF LIVER FIBROSIS IN CHRONIC HEPATITIS B PATIENTS

A liver biopsy is the gold standard for diagnosing and staging liver fibrosis in chronic hepatitis B patient but with many disadvantages so it is difficult to use as a routine examination. Research on index based on serum marker is helpful in predicting liver fibrosis. We conducted a study of the alpha-fetoprotein (AFP) and partial activated thromboplastin time (APTT) index or AA index in relation to the degree of liver fibrosis in chronic hepatitis B patients. This study was a retrospective cross-sectional study in dr.Wahidin Sudirohusodo Hospital Makassar by taking the data from medical records of chronic hepatitis B patients from January 2015 to December 2016. Samples were chronic hepatitis B patients who were tested for AFP, APTT and Fibroscan. The result showed the total of 79 chronic hepatitis B patients, 23 with severe fibrosis, 9 with moderate fibrosis, 26 with mild fibrosis, and 21 with no fibrosis. Spearman correlation test showed a significant correlation between the AA index and the degree of fibrosis (p &lt;0.001) and showed a positive correlation between both of them with a very strong correlation (r = 0.830). Oneway Anova test showed a significant difference between the AA index and the degree of fibrosis (p&lt;0.001). The results of this study indicate that the AA index can be used as a predictor of fibrosis in chronic hepatitis B patients. It is suggested to do another study with larger sample based on the degree of fibrosis.

Preperitoneal fat as a non‐invasive marker of increased risk of severe non‐alcoholic fatty liver disease in patients with type 2 diabetes

Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes. This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome. Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P=0.004) and liver fibrosis (P=0.008 and P=0.037, respectively). All fat areas correlated well with steatohepatitis (P≤0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2=0.379) and fibrosis (R2=0.181), respectively. Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver disease.

Serum ferritin as a non-invasive marker in the prediction of hepatic fibrosis among Egyptian patients with non-alcoholic fatty liver disease.

Background and AimMany studies have found a relationship between hepatic iron, serum ferritin, and non‐alcoholic fatty liver disease (NAFLD) or its progress. The aim of this study is to assess the value of serum ferritin as a non‐invasive marker in the prediction of hepatic fibrosis in NAFLD.MethodsThis study included 113 subjects who were classified into three groups. Group I included 30 healthy subjects as control with no clinical, radiological, and histological features of NAFLD. Group II included 31 NAFLD patients without hepatic fibrosis. Group III included 52 patients with hepatic fibrosis on top of NAFLD.ResultsSerum ferritin was determined using ferritin ELISA kit. Fibrosis 4 score was calculated. Liver biopsy was conducted for included patients. Significantly higher levels of serum ferritin were found in patients with hepatic fibrosis on top of NAFLD than controls. Receiver operating characteristic curve analysis revealed that an optimum cutoff level of 51.95 ng/mL was the best to predict fibrosis on top of NAFLD with diagnostic sensitivity and specificity of 65% and 60%, respectively, and area under the curve = 0.658.ConclusionHigher serum ferritin was found in patients with hepatic fibrosis on top of NAFLD. Serum ferritin was found to be a predictor of fibrosis on top of NAFLD with moderate sensitivity and specificity.

Predictors of Fibrosis in NAFLD Patients and the Impact of Statins on Outcomes

Predictors of Fibrosis in NAFLD Patients and the Impact of Statins on Outcomes

Can We Use Scd-163 in Combination with Other Noninvasive Fibrosis Markers to Predict Risky Esophageal Varices in Cirrhotics?

Background and aim: Still research is carried out for imaging and laboratory tools that can replace gastroscopy in esophageal varices prediction. Different non-invasive fibrosis predictors have shown promising results in predicting the presence of varices. In addition, serum sCD163 correlates with hepatic venous pressuregradient (HVPG). We had investigated different non-invasive tools for predicting the presence, size and/or bleeding risk of esophageal varices against gastroscopy as the gold standard as well as a stratification tool to identify patients who benefit from individualized surveillance or secondary prophylaxis.Methods: 243 cirrhotic patients were divided into three groups; group I: no varices, group II: small-sized varices, group III: mediumsized, large-sized and any size varices with risky signs. Assessment of sCD163 level, abdominal ultrasound and routine laboratory investigations were carried out. APRI, FIB-4, Lok’s score, Fibroindex, AAR and Platelet/spleen ratio were calculated and patients were monitored for one year. Band ligation was performed for significant varices and number of sessions and obliteration were recorded.Results: sCD163 levels were higher in patients having large varices (p=0.012), at risk of bleeding (p=0.04) and the bleeding patients (p=0.001). Lower albumin levels and platelets count, higher portal vein and splenic diameters, APRI, FIB4, Lok’s score, Fibroindex, AAR and platelet/spleen ratio were significant in patients with varices. Plt/spleen ratio had the best performance model in predicting varices using multivariate analysis with correct classification of 75.9%.Conclusion: Non-invasive fibrosis markers, especially the Plt/spleen diameter ratio; can predict the presence of esophageal varices; however, they still lack the specificity and sensitivity that make them replacing the screening endoscopy. Combining sCD163 to these tests may help in predicting bleeding risk. However, further studies are to be carved.

Clinical Presentation, Treatment Outcome and Predictors of Severity in Autoimmune Hepatitis: A Retrospective, Multicenter Experience

AIM: Autoimmune Hepatitis (AIH) is a chronic hepatitis of unknown etiology. It affects adults and children and can progress to cirrhosis. We aim to investigate the mode of presentation, predictors of severity and treatment outcome of AIH in Saudi patients. METHODS: This is a multicenter retrospective study that involved patients diagnosed with AIH from 3 tertiary hospitals. Clinical, biochemical, radiological and histopathological data were collected and treatment outcomes were reported. RESULTS: A total of 212 patients were included. Female: male ratio was 3:2 and the mean age was 36.2 ± 16.8 years while 50 patients (23.6%) were above age of 50. Abnormal liver function tests (LFTs) were found in (45%). Presentation was chronic in 37.7%, acute in 30.7%, with evidence of liver cirrhosis in 28.8% and with a fulminant disease in 2.8%. Antinuclear antibody (ANA) and Anti-smooth muscle antibody (ASMA) were negative in 65 (30.6%) and 74 (35%) patients respectively. Pre-treatment liver biopsies in 166 patients showed advanced fibrosis (stage 3 and 4) in 63.3%. On multivariate analysis, platelets, alanine transaminase (ALT) level and immunoglobulin G (IgG) level were predictors of fibrosis. Complete response was achieved in 74.5% while 9% had partial response and 16.5% had no response to treatment. CONCLUSION: The majority of AIH patients had advanced fibrosis at the time of diagnosis and liver cirrhosis was found in nearly one-third of cases. IgG, ALT, and platelet were predictors of advanced fibrosis. Complete response to treatment was achieved in two-third of patients. Relying on autoimmune markers for diagnosis can be misleading.

Pentraxin 3 Is a Predictor for Fibrosis and Arterial Stiffness in Patients with Nonalcoholic Fatty Liver Disease.

Objective. The aim of the present study was to investigate whether pentraxin 3 (PTX3) can be a new noninvasive marker for prediction of liver fibrosis in patients with NAFLD. We also aimed to evaluate the relationship between PTX3 and atherosclerosis in patients with NAFLD. Method. Fifty-four male patients with biopsy-proven NAFLD and 20 apparently healthy male volunteers were included. PTX3 levels were determined, using an ELISA method (R&D Sysytems, Quantikine ELISA, USA). To detect the presence of subclinical atherosclerosis in NAFLD, measurements of CIMT, FMD, and cf-PWV levels were performed. Results. PTX3 levels in NAFLD patients with fibrosis were higher than both NAFLD patients without fibrosis and controls (P = 0.032 and P = 0.028, respectively), but there was no difference between controls and NAFLD patients without fibrosis in terms of PTX3 levels (P = 0.903). PTX3 levels were strongly correlated with cf-PWV (r = 0.359, P = 0.003), whereas no significant correlation was found with other atherosclerosis markers, CIMT and FMD. Conclusion. Elevated plasma PTX3 levels are associated with the presence of fibrosis in patients with NAFLD, independently of metabolic syndrome components. This study demonstrated that for the first time there is a close association between elevated PTX3 levels and increased arterial stiffness in patients with NAFLD.

Carbohydrate Deficient Transferrin and Interleukin-6 as Predictors of Fibrosis in Alcohol Cirrhosis.

The severity of alcoholic cirrhosis depends on the presence of liver inflammation and fibrogenesis. Previous studies have hypothesized that carbohydrate deficient transferrin can be used as marker of liver impairment in alcoholic liver disease patients. The present study was designed to assess whether carbohydrate deficient transferrin is associated with procollagen III peptide and predict fibrosis in alcohol cirrhosis patients. We enrolled 48 patients with alcoholic cirrhosis and 38 healthy controls. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 levels were estimated in both groups. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 were significantly increased in alcoholic cirrhosis patients compared to controls. Stepwise regression analysis showed that carbohydrate deficient transferrin (adjusted R(2)=0.313, β=0.362, p=0.003) and interleukin-6 (adjusted R(2)=0.194, β=0.459, p=0.001) were positively associated with procollagen III peptide when age, duration and amount of alcohol consumption were considered as covariates. We conclude that elevated carbohydrate deficient transferrin and interleukin-6 act as predictors of fibrosis in alcoholic cirrhosis.