Hepatitis Monthly
Volume:21 Issue: 8, Aug 2021

There is a great need for further study on the mechanism of HCV infection or its pathopoiesis mechanism. Therefore, an HCV infection model was used to analyze the mechanisms of transcriptional and post-transcriptional regulation of gene expression.

The detections of transcriptome and microRNAs expressions in Huh7.5.1 cells infected with JFH-1 were conducted with next-generation sequencing. Moreover, bioinformatics data were obtained.

There were 21,827,299, and 42,588,251 reads qualified Illumina read pairs obtained from JFH-1-infected (HCV) and non-infected (blank) Huh7.5.1 cells, respectively. Moreover, 678 and 1,041 mRNAs data with a length of 101 bp from HCV and blank Huh7.5.1 cells cDNA sequence were generated, respectively. The results of comparative transcriptome sequencing analysis declared 460 differentially expressed mRNAs in HCV-infected cells, including 152 upregulated mRNAs and 308 downregulated mRNAs (HCV vs. blank). Gene Ontology (GO) and KEGG pathway enrichment analyses indicated the involved pathways, such as MAPK, p53, and PI3K/Akt signaling pathways, as well as oocyte meiosis and pathways in cancer.

Our work confirmed the transcriptome and microRNA data profiling from the cell model of HCV infection with JFH-1 using next-generation sequencing (NGS). Furthermore, the gene expression and regulation information or signaling pathways associated with the pathopoiesis mechanism of HCV infection were identified.

Accumulation of fat in the liver is one of the causes of non-alcoholic fatty liver disease (NAFLD), which affects about 30% of the world's population. Animal models have been useful tools for investigating the mechanisms involved in the etiology of NAFLD and developing new drugs.

This study aimed to present a new model for the detection of NAFLD in rats.

Forty-eight rats were randomly divided into six experimental groups: (1) control; (2) 45% fructose + 35% olive oil + carbon tetrachloride (FFC1); (3) carbon tetrachloride (1: 4 in olive oil) (C1); (4) carbon tetrachloride (1: 6 in olive oil) (C2); (5) 12.5% fructose + 12.5% olive oil (FF); and (6) 20% fructose + carbon tetrachloride (1: 4 in olive oil) (FC1). Blood samples were taken in three steps, and liver tissue was dissected at the end of the sixth week for histopathological assessments.

After six weeks, the alanine transaminase (131.63 ± 1.51), aspartate transaminase (275 ± 1.0), and gamma-glutamyl transferase (4.30 ± 0.1) levels increased significantly in the C1 group (P < 0.05). The serum lipid profile showed significant changes in all groups compared to the controls (P < 0.01). According to the histological results, all experimental groups, except the C2 group, showed symptoms of NAFLD; nevertheless, a higher NAFLD Activity Score (NAS) was found in the C1 group, followed by the FC1 group, compared to the other groups.

The present results revealed that injection of 0.1 mL/kg of carbon tetrachloride (C1 group), alone or along with a diet containing 20% fructose (FC1 group), provided useful animal models of NAFLD, although carbon tetrachloride injection alone is the most effective model in inducing NAFLD model that can be used as a new strategy in nutritional and pharmacological studies.
Keywords

Hepatitis C virus (HCV) could lead to increased mortality, disability, and liver transplant if left untreated, and it is associated with a possible increase in disease burden in the future, all of which would surely have a significant impact on the health system. New antiviral regimens in the treatment of the disease are effective yet expensive.

To performe a cost-effectiveness analysis of three medication regimens, namely, ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir, and daclatasvir/sofosbuvir (DCV/SOF) in HCV patients with genotype 1 in Iran.

A Markov model with a lifetime horizon was developed to predict the costs and outcomes of the three mentioned medication therapy strategies. The final outcome of the study was quality-adjusted life-years (QALYs) which was obtained using the previously published studies. The study was conducted from the perspective of the Health Ministry; therefore, only direct medical costs were estimated. The results were provided in the incremental cost-effectiveness ratio (ICER) per QALY. Ultimately, the one-way and probabilistic sensitivity analyses were used to measure the strength of study results.

The results showed that the QALY for LDV/SOF, DCV/SOF, and VEL/SOF were 13.94, 13.94, and 14.61, and the costs were 4807, 7716, and 4546$, respectively. The VEL/SOF regimen had lower costs and higher effectiveness than the LDV/SOF and DCV/SOF regimens, making it a dominant strategy. The tornado diagram results showed that the study results have the highest sensitivity to CHC and CC state costs. Moreover, the scatter plots results showed that VEL/SOF was the dominant therapeutic strategy in 73% of the simulations compared to LDV/SOF and in 66% of the simulations compared to DCV/SOF; moreover, it was in the acceptable region in 92% of the simulations and below the threshold. Therefore, it was considered the most cost-effective strategy. Moreover, the results showed that DCV/SOF was in the acceptable region below the threshold in 69% of the simulations compared to LDV/SOF. Therefore, DCV/SOF regimen was more cost-effective than LDV/SOF.

According to the present study results, it could be recommended that the VEL/SOF regimen be used as the first line of therapy in patients with HCV genotype 1. Moreover, the second-line medication regimen was DCV/SOF.

Chinese herbal medicine (CHM) has been widely used by patients in China and results in unpredictable nephrotoxicity and hepatotoxicity effects.

We report the case of a postoperative 69-year-old female patient with ascending colon cancer who rapidly developed liver cirrhosis after 18 months of continued CHM administration. The patient underwent right hemicolectomy at the Fourth Hospital of Hebei Medical University in August 2019 due to ascending colon cancer; at that time, the patient had no signs of liver cirrhosis based on computed tomography (CT) and routine blood examination. Postoperatively, the patient continued CHM administration for 18 months. The patient then visited our hospital with complaints of jaundice, abdominal distension, and edema in both lower limbs. CT imaging showed cirrhosis of the liver, while gastroscopy showed mild esophageal varices. Blood examinations including routine blood, coagulation function, and liver function tests, and biomarkers of hepatic fibrosis also supported the diagnosis of liver cirrhosis. To the best of our knowledge, this is the first report of CHM-induced liver cirrhosis.

CHM administration possibly induces rapid liver cirrhosis within 18 months.

Hepatitis C Virus (HCV) treatment in people who inject drugs (PWID) is a key component of elimination models but PWID face substantial barriers to treatment access. Despite data showing treatment outcomes among PWID on medications for opioid use disorder (MOUD) are similar to non-PWID outcomes, few studies examine PWID treatment outcomes with only syringe services support.

To evaluate the effect of recruitment for HCV treatment with elbasvir/grazoprevir (E/G) in a syringe services program (SSP) as compared to an MOUD program for people with opioid use disorder.

This real-world, multi-site prospective open-label pilot study compares treatment of PWID with aspartate aminotransferase to platelet ratio (APRI) < 0.7 and genotype 1a, 1b, and 4 HCV with E/G, engaged in MOUD (n = 25) or an SSP (n = 25). The MOUD arm was enrolled through a federally qualified community health center and SSP arm through a nearby SSP. Prospective arms were compared to an academic hepatology clinic group (n = 50). Sustained virologic response at 12 weeks (SVR12), medication adherence, and treatment discontinuation were evaluated.

In the MOUD vs SSP arms, substance use throughout treatment was found in 36% (9/25) vs 100% (25/25); good adherence (> 90% pills taken) in 100% (25/25) vs 68% (17/25); treatment completion 100% (25/25) vs 64% (16/25); and SVR12 rates were 96% (24/25) vs 60% (15/25). In the community standard comparison group, SVR12 was achieved in 94% (47/50). There were two virologic failures or re-infections in the SSP group; all other non-responders were due to missing SVR12 data.

While recruitment and follow-up are challenging in SSPs, preliminary data suggests adherence, treatment completion, and SVR12 are high in PWID treated with E/G engaging in SSP or MOUD. All metrics are comparable to community standards for non-PWID for treatment of HCV with direct-antiviral drugs.