Liver Research最新文献

With the advent of the era of organ donation after citizen's death, split liver transplantation (SLT) can effectively increase the supply of donor livers and shorten the transplantation wait time for patients, especially pediatric recipients. In recent years, SLT has been performed to varying degrees in many transplant centers in China, and varying levels of efficacy have been achieved. The quality of donors and donor livers for SLT is an important factor affecting the outcome of the surgery. At this stage, it is necessary to reach a consensus on the evaluation of SLT donor and liver donor that is suitable for the conditions in China by combining the well-established experience of the international community with advanced transplantation technology. This approach will aid in enhancing the efficacy of SLT. Based on the experience of experts, a consensus on the evaluation of donors and donor livers for SLT has been formulated in this study, which focuses on evaluation of donors and donor livers, evaluating the functional and anatomical aspects of the donor liver and donor–recipient matching.

Background and aim

Liver fibrosis resulting from persistent liver injury represents a major healthcare problem globally. Traditional Chinese medicine has played an essential role in the treatment of liver fibrosis in recent years. Thus, this study aims to assess the effect of Longhu Rendan (LHRD), a Chinese traditional patent medicine, on liver fibrosis and its potential mechanism.

Methods

The liver fibrosis in mice was induced via the intraperitoneal injection of carbon tetrachloride (CCl₄) for 6 weeks or bile duct ligation for 15 days. Various methods were used to judge the therapeutic effect of LHRD.

Results

LHRD significantly suppressed the activity of serum index of abnormal liver function, liver cell apoptosis, and necrosis, attenuating liver injury. Moreover, LHRD treatment alleviated liver fibrotic features, such as the reduction of collagen deposition and hepatic stellate cell activation as well as profibrotic gene expression. Mechanistically, LHRD treatment inhibited nuclear transcription factor-kappa B signaling and inflammatory gene expression and diminished the production of reactive oxygen species and 4-hydroxynonenal, along with the downregulation of NADPH oxidase 4.

Conclusions

Overall, the present study demonstrates that LHRD ameliorates liver injury and fibrosis via the inhibition of inflammation and oxidative stress in mice, indicating that LHRD is a potential medicine for the treatment of liver fibrosis.

Erythropoietic protoporphyria (EPP) is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase (FECH), resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissues. Here, we report a patient with photosensitive dermatitis and acute icteric hepatitis caused by EPP, whose clinical and biochemical results successfully improved following 2-month treatment with glucose load, ursodeoxycholic acid capsules, and cholestyramine powder. This case provides a reference for a combination therapy strategy for patients with liver and skin injury caused by EPP.

Background and aim

Whereas Yttrium-90 selective internal radiation therapy (Y-90 SIRT) was shown to improve local tumor control in non-Asian population, the efficacy of this therapy for Asian population in real-world setting remains poorly detailed. We aimed to determine outcomes and identify predictors of response in hepatocellular carcinoma (HCC) patients treated by Y-90 SIRT.

Methods

We retrospectively enrolled 52 HCC patients receiving Y-90 SIRT at our tertiary center between 2014 and 2019. Overall survival (OS), progression free survival (PFS), and predictive factors were determined by Kaplan–Meier method and Cox-proportional hazard analysis.

Results

Of the 52 patients (81% male, mean age 64.9 years), 71% and 29% were classified as Barcelona Clinic Liver Cancer stage C and B HCC, respectively; 63% had portal vein thrombosis, and 35% had objective tumor response defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. OS and PFS were 11.0 and 2.4 months, respectively. Two patients were successfully down-staged and further underwent surgical resection. Multifocal lesion, alpha-fetoprotein (AFP) ≥200 ng/mL, and Eastern Cooperative Oncology Group (ECOG) score ≥1 were significantly associated with poor survival, with adjusted hazard ratio (95% confidence interval) of 7.7 (2.0–29.8), 5.4 (2.0–14.7), and 3.1 (1.0–9.6), respectively (all in P < 0.05).

Conclusions

Y-90 SIRT is an effective treatment for the local tumor control of HCC without serious adverse events. Single lesion, AFP level and ECOG status were predictors of response.

Background and aim

Several effective antiviral drugs are now available; however, the risk of liver-related complications is still present. Low-level viremia (LLV), defined as a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load lower than 2000 IU/mL, is one of the major factors responsible for these complications. It has been reported that 22.7–43.1% of patients with HBV experience LLV. Herein, we aimed to explore the risk factors for very LLV (VLLV) during antiviral treatment.

Methods

We collected data of patients with chronic hepatitis B (CHB) who received nucleos(t)ide analog treatment from October 2016 to April 2021. VLLV was defined as an HBV DNA load of 9–20 IU/mL. A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.

Results

Seropositivity rates for hepatitis B e antigen (HBeAg) (45.3% vs. 17.3%, P < 0.001) and hepatitis B surface antigen (HBsAg, 3.11 ± 0.68 lg IU/mL vs. 2.54 ± 1.04 lg IU/mL, P < 0.001) and alanine aminotransferase levels (30.34 ± 15.08 U/L vs. 26.15 ± 16.66 U/L, P = 0.040) in the two groups were significantly different. The multivariate analysis showed that both HBeAg seropositivity (adjusted odd ratio (aOR), 3.63; 95% confidence interval (CI): 1.98–6.64; P < 0.001) and HBsAg levels (aOR, 2.21; 95% CI: 1.53–3.20; P < 0.001) are independent risk factors for VLLV. During the multivariate analysis in the subgroup of HBeAg-positive patients, male gender (aOR, 3.68; 95% CI: 1.23–10.76; P = 0.017) and high HBsAg (aOR, 4.86; 95% CI: 1.73–13.64; P = 0.003) levels were significantly correlated with VLLV. However, this was not the case in HBeAg-negative patients (P > 0.050). HBeAg seropositivity (aOR, 5.08; 95% CI: 2.15–12.02; P < 0.001 vs. aOR, 2.78; 95% CI: 1.16–7.00; P = 0.022) and HBsAg levels (aOR, 2.75; 95% CI: 1.41–5.37; P = 0.003 vs. aOR, 2.10; 95% CI: 1.27–3.46; P = 0.004) significantly increased the risk of VLLV, irrespective of the age group. Both HBsAg (area under the receiver operating characteristic curve (AUC), 0.681; 95% CI: 0.623–0.736; P < 0.001) and HBeAg (AUC, 0.640; 95% CI: 0.581–0.697; P < 0.001) had certain predictive value for VLLV.

Conclusion

HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence. When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks, emphasis should be placed on the potential occurrence of VLLV, warranting the use of highly sensitive HBV DNA detection methods.

Alcohol-related liver disease (ALD), which is caused by excessive alcohol consumption, is one of the most common types of liver disease and a primary cause of hepatic injury, with a disease spectrum that includes steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Various lines of evidence have indicated that immune cells play a significant role in the inflammatory processes of ALD. On the one hand, the liver contains various resident immune cells that have been proven to perform different functions in ALD. For example, in the progression of the disease, Kupffer cells (KCs) are activated by lipopolysaccharide-Toll-like receptor 4 signaling and release various proinflammatory cytokines. Moreover, alcohol intake has been shown to depress the function of natural killer cells. Additionally, two types of unconventional T cells (natural killer T cells and mucosal-associated invariant T cells) are involved in the development of ALD. On the other hand, alcohol and many different cytokines stimulate the recruitment and infiltration of circulating immune cells (neutrophils, T cells, macrophages, and mast cells) into the liver. The neutrophils can produce proinflammatory mediators and cause the dysfunction of anti-infection processes. Additionally, alcohol intake can change the phenotype of T cells, resulting in their increased production of interleukin-17. Aside from KCs, infiltrating macrophages have also been observed in patients with ALD, but the roles of all of these cells in the progression of the disease have shown both similarities and differences. Additionally, the activated mast cells are also associated with the development of ALD. Herein, we review the diverse roles of the various immune cells in the progression of ALD.

Portopulmonary hypertension (POPH) is a severe pulmonary vascular disease secondary to portal hypertension and a subset of Group 1 pulmonary hypertension (PH). The pathological changes of POPH are indistinguishable from other PH phenotypes, including endothelial dysfunction, pulmonary vasoconstriction, and vascular remodeling. These changes cause a progressive increase in pulmonary vascular resistance and afterload of the right ventricle, eventually leading to severe right heart failure. The prognosis of POPH is extremely poor among untreated patients. POPH is associated with a high risk of death after liver transplantation (LT), and severe POPH is considered an absolute contraindication for LT. However, pulmonary arterial hypertension (PAH)-targeted therapies are administered to patients with POPH, and aggressive drug treatment significantly optimizes pulmonary hemodynamics and reduces the risk of death. Therefore, early diagnosis, aggressive PAH-targeted therapies, and proper selection of liver transplant candidates are vital to reduce the risk of surgery and improve clinical outcomes. This article aims to review the results of previous studies and describe biological mechanisms, epidemiology, potential risk factors, and diagnostic approaches of POPH. Moreover, we introduce recent therapeutic interventions for the early diagnosis of POPH and efficient clinical management decisions.

Background and aim

Severe alcoholic hepatitis (SAH), the most florid form of alcohol-related liver disease (ALD), has a mortality rate of 16% at 28 days. The angiopoietin-Tie 2 system regulates angiogenesis and inflammation, both of which are implicated in the pathogenesis of ALD. This study examined plasma and hepatic gene expression of angiopoietin 1 (ANG1) and angiopoietin 2 (ANG2) in patients with SAH and ALD and investigated their roles as prognostic biomarkers.

Methods

A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay (ELISA) from 30 patients with SAH (Maddrey's discriminant function ≥32), 32 patients with ALD cirrhosis and 15 healthy controls (HC). RNA sequencing for ANG1, ANG2, TIE1 (codes for Tie1 receptor) and TEK (codes for Tie2 receptor) gene expression from a separate cohort study of 79 patients was also performed.

Results

Plasma levels of ANG1 were lower (P = 0.010) and ANG2 were higher (P < 0.0001) in patients with ALD/SAH compared to HC. The ANG2: ANG1 ratio was higher in those with ALD/SAH compared to HC (P < 0.0001). ANG2 levels were the highest in patients who developed sepsis (P = 0.030) and those dying within 90 days (P = 0.020). ANG2 levels correlated positively with model for end-stage liver disease (MELD) score (r = 0.30, P = 0.020), Child-Pugh score (r = 0.38, P = 0.003), international normalized ratio (r = 0.41, P = 0.001) and white blood cell count (r = 0.28, P = 0.040) and inversely correlated with albumin (r = −0.26, P = 0.040).

ANG1 gene expression from liver biopsies was higher in SAH than that in HC (P < 0.0001), and greater in severe disease (P < 0.0001). ANG2 gene expression trended towards being lower in SAH than that in HC (P = 0.070) though was upregulated in severe disease (P = 0.0003).

Conclusions

Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.

The 4th Chinese American Liver Society (CALS)/Society of Chinese Bioscientists in America (SCBA) Hepatology Division Annual Symposium was held virtually on October 29–30, 2021. The goal of the CALS Symposium was to present and discuss the recent research data on the pathogenesis and therapeutic targets of liver diseases among the CALS members, trainees and invited speakers. Here we briefly introduce the history of the CALS/SCBA Hepatology Division and highlight the presentations that focus on the current progresses on basic and translational research in liver metabolism, bile acid biology, alcohol-related liver disease, drug-induced liver injury, cholestatic liver injury, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and liver cancer.