MELD or MELD-Na as a Predictive Model for Mortality Following Transjugular Intrahepatic Portosystemic Shunt Placement.

Background and Aim: The model for end-stage liver disease (MELD) was originally developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS). The MELD-sodium (MELD-Na) score has replaced MELD for organ allocation for liver transplantation. However, there are limited studies to compare the MELD with MELD-Na to predict mortality after TIPS. Methods: We performed a retrospective chart review of patients who underwent TIPS placement between 2006 and 2016 at our institution. The primary outcome was mortality, and the secondary outcomes sought to assess which variables could provide prognostic information for mortality after TIPS placement. We performed receiver operating characteristic (ROC) curve analysis to assess the performance of MELD and MELD-Na. Results: There were 186 eligible patients in the analysis. The mean pre-TIPS MELD and MELD-Na were 13 and 15, respectively. Overall, mortality after TIPS was 15% at 30 days and 16.7% at 90 days. In a comparison of the areas under the ROCs for MELD and MELD-Na, MELD was superior to MELD-Na for 30-day (0.762 vs. 0.709) and 90-day (0.780 vs. 0.730) mortality after TIPS. The optimal cutoff score for 30-day mortality was 15 (0.676-0.848) for MELD and 17 (0.610-0.808) for MELD-Na, whereas the optimal cutoff score for 90-day mortality was 16 (95% CI: 0.705-0.855) for MELD and 17 (95% CI: 0.643-0.817) for MELD-Na. There were 24 patients with high MELD-Na ≥17, but with low MELD <15, and 90-day mortality in this group was 8.3%. Conclusions: Although MELD-Na is a superior prognostic tool to MELD for predicting overall mortality in cirrhotic patients, MELD tended to outperform MELD-Na to predict mortality after TIPS.

Using vibration controlled transient elastography and FIB-4 to assess liver cirrhosis in a hepatitis C virus infected population.

ABSTRACT: We assessed the performance characteristics of the Fibrosis-4 (FIB-4) score in a veteran population with chronic hepatitis C virus (HCV) infection and used vibration controlled transient elastography (VCTE) as the gold standard.All VCTE studies were performed by a single operator on United States veterans with HCV infection presenting for care at the Atlanta VA Medical Center (AVAMC) over a 2 year period. VCTE liver stiffness measurements (LSM) were categorized as cirrhotic if LSM was >12.5 kPa and non-cirrhotic if LSM was ≤12.5 kPa. FIB-4 scores ≤3.25 were considered non-cirrhotic and scores >3.25 were considered cirrhotic. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the FIB-4 score. A second analysis was done which identified and excluded indeterminate FIB-4 scores, defined as any value between 1.45 and 3.25.When FIB-4 was used to screen for liver cirrhosis using VCTE as the gold standard, sensitivity was 42%, specificity was 88%, PPV was 62%, and NPV was 76%. When indeterminate FIB-4 scores were excluded from the analysis, sensitivity was 95%, specificity was 61%, PPV was 62%, and NPV was 94.4%. In a veteran population with chronic HCV infection, we found the sensitivity of the FIB-4 score to be unacceptably low for ruling out liver cirrhosis when using a binary cutoff at 3.25. Using a second staging method like VCTE may be an effective way to screen for liver cirrhosis in persons with chronic HCV, especially when the FIB-4 score is in the indeterminate range.

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data.

AIM: To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. RESULTS: A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. CONCLUSION: Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.

Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data.

AIM: To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients. METHODS: Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS: The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies. CONCLUSION: Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.

Current Management of Alcoholic Hepatitis and Future Therapies.

Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply.

The impact of functional constipation on quality of life of middle-aged Black Americans: a prospective case-control study.

PURPOSE: To quantify the impact of constipation on health-related quality of life (HRQoL) in Black Americans. METHODS: Case-control design. Black subjects referred for colon cancer screening with a Bristol Stool Score of 3-5 for >75% of bowel movements served as controls. Frequency-matched functional constipation subjects had to fulfill Rome III criteria. Both groups completed demographic and health surveys. Short Form-36 assessed HRQoL. RESULTS: We recruited 102 constipated patients and 100 controls. The groups were well matched demographically. After adjustment for comorbidities, SF-36 scores for vitality, bodily pain, social functioning, and role-emotional were significantly lower in constipated patients. Unadjusted physical and mental component summary scores (PCS and MCS) were significantly higher in the control group (47.1 ± 10.6 vs. 43.3 ± 8.6; P = 0.005 and 50.6 ± 12.4 vs. 43.4 ± 11.8; P < 0.001, respectively). After adjustment for comorbidities, PCS differences were no longer significant (P = 0.54); however, MCS differences were significant (P = 0.004). Marginal mean scores for the MCS for controls and constipated subjects were 49.9 ± 1.2 and 43.6 ± 1.2, respectively. The presence of a comorbidity was independently associated with PCS (P < 0.001) and MCS (P = 0.026) results. CONCLUSIONS: Functional constipation has a significant impact on HRQoL in middle-aged Black Americans, particularly in regard to mental well-being.

Rabeprazole: a pharmacologic and clinical review for acid-related disorders.

Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of approximately 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.