Hepatitis Monthly
Volume:21 Issue: 4, Apr 2021

 Sarcopenia, defined as low muscle mass with reduced function, is frequently encountered in cirrhotic patients and is a major predictor of adverse events, including post-liver transplant (LT) outcome.

 This study assessed the impact of sarcopenia using computed tomography (CT)-based measurements on post-LT mortality and complications.

 From January 2008 to June 2016, 646 adult patients underwent 613 LTs at our institution. We analyzed the postoperative outcome of 287 patients who had pathologically proven cirrhosis on the explanted liver and who had performed a CT examination three months before LT. Psoas muscle density (PMD) was detected for every patient using standard instruments present in the radiological workstation and was related to postoperative survival rates and complications. Statistical analysis was carried out using the appropriate tests.

 Postoperative mortality was 6.3%. At least one grade III-IV postoperative complication was experienced by 121 patients. Respiratory and infective complications occurred in 30 and 32 patients, respectively. Also, PMD was an independent predictor of postoperative mortality (P = 0.021), respiratory complications (P = 0.015), and infections (P = 0.010). The ROC analysis identified a PMD ≤ 43.72 HU as the best cutoff value for predicting 90-day mortality after LT.

 Psoas muscle density accurately predicted post-LT mortality and complications. Its ease and low-cost determination can allow widespread use of this parameter to improve clinical care and help with the decision to give these patients some priority on the transplant waiting list.

Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection.

To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection.

In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment.

All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required.

Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.

 Hepatic epithelioid hemangioendothelioma (HEHE) is a discrete vascular tumor with an unpredictable natural course. This rare tumor is commonly found incidentally and not too often is mistaken radiologically and histologically for another tumor. No single treatment strategy has yet been established for it, partly due to its variable clinical course, ranging from an indolent tumor with prolonged survival to an aggressive, fatal disease.

 Among 1,029 liver transplantation cases performed at our hospital between January 2001 and November 2019, three were done for HEHE. In this study, we present these three cases and review their clinical and histopathologic characteristics.

 Epithelioid hemangioendothelioma (EHE) of the liver is a low-grade malignant tumor with different presentations, treatment strategies, and outcomes. The histopathologic characteristics of HEHE can hide its vascular nature, thus leading to its confusion with other lesions. This tumor is unique in that its clinical and histopathologic features do not always correlate with its biologic behavior. There are no reliable criteria in predicting the clinical outcome of HEHE, which needs further research.
 

 Hepatic stellate cells (HSCs) are liver-specific pericytes that transform into myofibroblasts, which are involved in pathological vascularization in liver fibrosis. We previously suggested that A20 overexpression suppresses lipopolysaccharide (LPS)-induced inflammation in HSC. We aimed to determine the mechanisms of the anti-inflammatory role of A20 in LX-2 cells.

 LX-2 cells were transfected with A20-siRNA or control-siRNA and control adenovirus or A20-carrying adenovirus. Quantitative reverse transcription PCR (RT-qPCR) analysis was employed to quantify mRNA levels of α-SMA, col-I, col-III, IL-6, TGF-β, and PDGF in A20-siRNA LX-2 cells stimulated with LPS. Multiple molecular indices of MAPK/ERK/JNK signal pathway were performed by using gene transfection and Western blotting.

 Relative to control, the fibrosis-related mRNA levels of α-SMA, col-I, and col-III were increased in A20-siRNA LX-2 cells. Meanwhile, A20-siRNA cells significantly increased IL-6, TGF-β, and PDGF mRNA levels. Relative to controls, stimulating A20 overexpressing LX-2 cells with LPS for 5 and 30 minutes significantly reduced the levels of phosphorylated ERK and JNK, respectively. A20 knockdown in LX-2 cells promotes phosphorylated ERK and JNK levels with LPS for 30 minutes.

 Our data indicate that A20 could be functional in HSCs through the MAPK/ERK/JNK signaling pathway, highlighting a potential novel therapeutic strategy against liver fibrosis.

 Liver fibrosis is often attributed to the activation of hepatic stellate cells (HSCs) and excessive scar formation in the liver. Advanced stages of the disease often lead to liver cirrhosis and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) is a secreted protein, which has anti-diabetic and lipocaic effects.

 In this study, we investigated the ability of FGF21 to reduce hepatic fibrogenesis due to the accumulation of free cholesterol in the LX2 cell line (a type of HSC-derived cell line) and its mechanism of action.

 Cells were treated with 25, 50, 75, and 100 μM concentrations of cholesterol for 24 and 48 h. The mRNA expression of genes of TGF-β, αSMA, and collagen1α and the level of Smad3C protein were measured to assess liver fibrosis. Next, the cells were treated with FGF21 for 24 h, and the expression levels of TGF-β, αSMA, collagen 1α, and Smad3C protein were measured.

 The results showed that the expression of TGF-β, αSMA, collagen 1α genes, and also the level of Smad3C protein in the presence of cholesterol increased significantly compared to the control group. Treatment with FGF-21 also significantly reduced the expression of TGF-β, αSMA, and collagen 1α genes.

 Cholesterol by increasing the level of Smad3C protein and activating the TGF-β signaling pathway increases major proteins involved in the production of extracellular matrix, including collagen 1α. Besides, FGF21 inhibits the further activation of HSCs by inhibiting the TGF-β/Smad3C signaling pathway and thus can prevent the progression of liver fibrosis.