Introduction

In Italy, the prevalence of HDV infection in HBsAg carriers is about 9.9% (6.4% in Italian natives and 26.4% in immigrants). However, the actual prevalence is underestimated because the anti-HDV test is not performed routinely in all HBsAg carriers.

Aims & Methods

The aim of this study was to compare the prevalence and the absolute number of HDV infection identified in HBsAg-positive subjects tested at University Hospital Federico II before and after the introduction of anti-HDV reflex testing.
​From January to December 2022, reflex test for the detection of total HDV antibodies was performed in all HBsAg positive subjects observed at AOU Federico II. We used as control group the HBsAg-positive subjects tested at the same laboratory between January and December 2019, before the implementation of anti-HDV reflex testing. Sera were evaluated with ADVIA Centaur HBsAgII Qualitative, Liaison Murex HBsAg Quantitative and Liaison Murex Total Anti-HDV Qualitative.

Results

Before reflex testing, anti-HDV had been tested in 16.4% (84/512) of HBsAg positive subjects, while after its implementation, 100% (484/484) of HBsAg positive patients was tested for anti-HDV. The anti-HDV positive prevalence was lower than before the introduction of reflex test (10.7% vs 16.6%), but the absolute number of anti-HDV positive patients increased (14 vs 52 subjects). HDV-RNA was detectable in 26 (53%) of 49 subjects tested.

Conclusion

Our data showed that the implementation of anti-HDV reflex testing increased the number of diagnosis of HDV infection. In this setting, due to the forthcoming approval of specific anti-HDV drugs, a reflex test for anti-HDV should be implemented, in clinical practice, to early identify patients with HBV/HDV infection.

Introduction

Renal dysfunction in the presence of end stage liver disease (ESLD) has been associated with increased morbidity and mortality post liver transplant (LT). In the presence of concomitant renal disease, pre-LT renal replacement therapy (RRT) has demonstrated improved outcomes post-LT. However, the role of RRT prior to LT in patients without renal disease is arguable.

Aims & Methods

In this study, we aimed to study the outcomes of RRT initiated pre-LT in patients awaiting LT without renal disease. US nationwide readmission database (NRD 2016 to 2019) was used. Hospitalizations that underwent RRT before liver transplant (cases) were identified using the database. A matched comparison cohort of similar hospitalizations who did not undergo RRT before liver transplant (controls) was identified from NRD after 1:1 propensity score matching.
After identifying the index admission from NRD, we calculated the time to RRT and time to LT using procedure codes and study patients were included only if time to RRT was less than time to LT, thereby correctly identifying patients who had RRT pre-LT. Inpatient clinical outcomes, mortality and survival estimates were calculated and compared. Hospitalizations with age<18 years, end-stage renal disease (ESRD) or CKD stage IV, renal transplant were excluded from the analysis.

Results

728 patients were included. We matched 364 hospitalizations with RRT before LT (cases) to 364 hospitalizations with no RRT before LT (controls). Adequate comorbidity balance was achieved with propensity matching between the comparison groups, including CKD (stage I - III), obesity, fluid & electrolyte disorder. The median age was 51.5 years in cases (IQR 43-59) and 54 years in controls (IQR 46-61). The time to liver transplant was longer in patients with pre-LT RRT as compared to no RRT before LT [13.5 days (IQR 8-20) vs 1 day (IQR 0-8), P<0.001].
There was no statistical difference in all-cause inpatient mortality between cases and controls (4.9% vs. 3.6%, P=0.4). Pre-LT RRT was associated with longer length of stay, 32 days (IQR 22-46) compared to 14 days (IQR 9-30) (P<0.001) in patients without pre-LT RRT. Additionally, the median total hospital charges were also higher in pre-LT RRT [$827,695 (IQR 574,184-1,354,623) vs $467,809 (IQR 323,809-724,291), P<0.001].
A significantly greater proportion of patients with RRT prior to LT were associated with mechanical ventilation (43.7% vs. 16.2%, OR 4.0 [2.8- 5.7], P<0.001), septic shock (44.8% vs. 21.4%, OR 2.9 [2.1- 4.1], P<0.001), ICU admission (40.7% vs. 17.0%, OR 3.3 [2.4- 4.7], P<0.001), vasopressor requirement (23.9% vs. 14.3%, OR 1.9 [1.3 - 2.8], P<0.001) and acute kidney injury (95.6% vs. 75.8%, OR 6.9 [3.9 - 12.1], P <0.001) as compared to controls. RRT requirement post LT was significantly greater in cases vs controls (100% vs 17%, P<0.001).
There was no difference in transplant rejection (5.2% vs 6%, p=0.6), risk of inpatient mortality at 30-day (HR 1.06 [0.4-2.6], P=0.9), 60-day (HR 0.85 [0.4-1.8], P=0.7) or 90-day intervals (HR 0.79 [0.4-1.6], P=0.5) (Figure 2) between the groups. 180-days Kaplan-Meier survival estimates were comparable as well (P=0.5).

Conclusion

Based on this study, RRT prior to LT was associated with greater instances of ICU related treatment, AKI and need for RRT post-LT. LT rejection, 30-day, 60-day and 90-day inpatient mortality were similar, along with comparable 180-day survival estimates. Results seem to suggest RRT is better avoided in pre-LT setting in the absence of renal dysfunction. Longitudinal studies are warranted to establish causality.

Introduction

The passive bending colonoscope (PBCS) has a passive bending section on the scope head that could make the scope advance deeply and smoothly without forming a walking-stick handle. Although the efficacy of PBCS as colonoscope has been presented^1-3, the utility in endoscopic retrograde cholangiopancreatography (ERCP) for the patients with surgically altered anatomy (SAA) has not been established. There is no large-scale studies exist to date and only a case series that described the effect of PBCS-ERCP for patients with SAA was reported⁴.

Aims & Methods

We performed a multicenter observational study to evaluate the outcome of PBCS-ERCP compared to balloon assisted enteroscope (BAE) ERCP that could expand the drainage options for SAA cases. This study involved 343 patients with SAA who underwent ERCP. Among them, 110 underwent PBCS-ERCP, while 233 underwent BAE-ERCP. Propensity score matching was applied and a final cohort of 210 (105 in each group) with well-balanced backgrounds (type of SAA, presence of stomach, presence of naïve papilla Vater, Age and sex) was analyzed. In this study, CF HQ290ZI (similar to CF-HQ190I) and PCF PQ260L (similar to PF-PH190L) (Olympus Medical Systems, Tokyo, Japan) were used as PBCS. As BAE, EI580BT double balloon enteroscope (Fujifilm, Tokyo, Japan) was used.We evaluated the success rate and time to reach the anastomosis or ampulla of Vater as a primary outcome. Other success rate (cannulation, completion of planned procedure) and incidence of adverse event was also analyzed as secondary outcome measure.

Results

The success rate for reaching was 91.4% (96/105) in PBCS and 90.5% (95/105) in BAE (odds ratio [95%CI]: 1.12, [0.44–2.89], p = .809). Mean required time to reach was 10.04 min. (SD, 9.62) in PBCS, 18.77 min. (SD, 13.21) in BAE and significantly shorter in PBCS (p < .001). The success rate to cannulate and complete the procedure was not significantly different (cannulation, 97.8% in the PBCS and 90.2% in the BAE, odds ratio [95%CI]: 4.88, [1.02–23.24], p = .062; completion, 88.6% in PBCS and 81.0% in BAE, odds ratio [95%CI]: 1.82, [0.84–3.95], p = .178), while the required time to cannulate and complete the procedure was significantly shorter in PBCS (cannulation, 2.7 min. (SD, 3.16) in PBCS, 7.13 min. (SD, 9.71) in BAE, p < .001; completion, 42.32 min. (SD, 25.15) in PBCS, 65.73 min. (SD, 31.23) in BAE, p < .001). The incidence of adverse event was significantly higher in BAE (20/105, 19.0%) than in PBCS (5/105, 4.8%) (p < .001).

Conclusion

PBCS-ERCP showed promising results for SAA cases with shorter procedure time and lower adverse event incidence compared to BAE-ERCP, despite no significant difference in success rates.

References

1. Mizukami T, Ogata H, Hibi T. "Passive-bending colonoscope" significantly improves cecal intubation in difficult cases. World J Gastroenterol 2012;18:4454-6.
2. Sato K, Shigiyama F, Ito S, et al. Colonoscopy using a small-caliber colonoscope with passive-bending after incomplete colonoscopy due to sharp angulation or pain. Surg Endosc 2013;27:4171-6.
3. Sato K, Ito S, Shigiyama F, et al. A prospective randomized study on the benefits of a new small-caliber colonoscope. Endoscopy 2012;44:746-53.
4. Nakaji S, Hirata N, Shiratori T, et al. Three successful cases of biliary tract disease with Roux-en-Y reconstruction treated by ERCP using PCF-PQ260L. JJBA 2014;28:89-94.(in Japanese)

Introduction

The clinical value of combined resection of important hepatic vessels in hilar cholangiocarcinoma remains controversial. We aimed to compare the short-term and long-term outcome of combined versus non-combined major vessel resection in patients undergoing radical resection for hilar cholangiocarcinoma.

Aims & Methods

This single centre retrospective cohort study of patients with hilar cholangiocarcinoma was conduct from January 2007 to December 2018. Patients who underwent radical re-resection were enrolled. The short-term and long-term clinical outcomes of the groups were compared after propensity score matching.

Results

A total of 310 patients were included. There was no statistically significant difference in perioperative clinical outcomes between VR group (PVR and AVR) and non-VR group after 1:2 PSM. Patients who received PVR had significantly longer OS (p=0.023) and DFS (p=0.010) compared to those in the non-PVR group. AVR group was associated with improved OS (p=0.036) and DFS (p=0.029) compared with non-AVR group following the curative-intent resection. The postoperative complications of combined VR would not worsen long-term survival for patients (OS: p=0.159; DFS: p=0.112).

Conclusion

Combined vascular resection (VR) would improve the long-term survival for patients with hilar cholangiocarcinoma. The postoperative complications of combined VR would not worsen long-term survival. Therefore, radical surgical resection should be actively performed in these patients.

Disclosure

The authors declare that they have no competing interests.

Introduction

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by liver steatosis and inflammation which abnormal immune responses involved in pathogenesis, and there is no approved therapeutic drug. Rhein, one of the main bioactive components of Rheum palmatum, has exerted anti-inflammatory properties. However, the mechanism by which Rhein exerts beneficial effects against NASH is far from elucidated. Here, our study aimed to investigate the therapeutic effects of Rhein on liver steatosis and inflammation and elucidate the related mechanisms of immunoregulation.

Aims & Methods

Male C57BL/6 mice were given high-fat diet for 10 weeks to induce NASH, followed by Rhein suspension administration at a dose of 100mg/kg and 200mg/kg for 4 weeks. The therapeutic effect of NASH was estimated by body weight, liver weight, LW/BW, food intake, the liver appearance and the histological analysis of liver section stained with hematoxylin and eosin. The proportion of lymphocyte cells in the mesenteric lymph nodes (MLNs) was detected by flow cytometry.

Results

Our findings demonstrated that high-fat diet treatment resulted in severe liver inflammation and severe steatosis, while Rhein appreciably reverse these phenomenon, as evidenced by the reduction of body weight, liver wet weight, LW/BW, and liver size in mice. Histological analysis of liver section revealed that administration of Rhein exhibited improvement of severe steatosis, elimination of inflammatory cells and resolution of balloon-like changes when compared to mice in the HFD group. Interestingly, there were no significant differences in food intake among groups of mice, suggesting that the protective effect of Rhein is not achieved by inhibiting appetite. Mechanistically, flow cytometry analysis showed that higher Th1 and Th17 polarized response were detected in the MLN compartments in HFD-induced mice, evidenced by the detection of increased numbers of Th1 cells (CD3+CD4+IFN-γ+) and Th17 cells (CD3+CD4+IL-17+), and Rhein intervention showed significant decrease numbers of Th1 and Th17 in MLNs. In contrast, Rhein treatment significantly increased the numbers of Treg cells (CD3+CD4+Foxp3+) with anti-inflammatory effects in the MLN of NASH mice.

Conclusion

Our results provide novel insights into the protective role of Rhein in modulating the liver steatosis and inflammation, with therapeutic potential for immunology-targeted strategy in the treatment of NASH.

References

[1] Cheng L, Chen Q, Pi R, Chen J. A research update on the therapeutic potential of rhein and its derivatives. Eur J Pharmacol. 2021,899:173908. doi:10.1016/j.ejphar.2021.173908.
[2] Gebru YA, Gupta H, Kim HS, et al. T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2021,22(22):12190. doi:10.3390/ijms222212190

Disclosure

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Introduction

The literature regarding the risk of progression to extrahepatic disease and clinical factors associated with the development of metastases in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is sparse.

Aims & Methods

We aimed to assess the incidence of extrahepatic recurrence and to identify clinically relevant risk factors for the development of metastases in patients with HCC treated with TACE as first-line treatment.
From the Italian Liver Cancer (ITA.LI.CA) database, data of 981 HCC patients undergoing TACE as first-line treatment were retrieved and retrospectively analyzed. Incidence of extrahepatic recurrence was compared between two groups according to the diameter of the largest liver lesion at the time of TACE (HCC ≤ 3 cm vs. HCC > 3 cm). Multivariate Cox regression was used to identify predictor of extrahepatic recurrence.

Results

During a median follow-up of 27.0 months (IQR, 13.2-49.0) the overall recurrence rate was 75.4%. Only 78/981 patients (8.0%) had an extrahepatic tumor localization at first recurrence (5.4% in the ≤3 cm group and 10.7% in the >3 group; p=0.002), while the overall extrahepatic recurrence rate was 26.0% (21.2% and 31.0% patients in the ≤3 cm and >3 cm groups, respectively; p=0.0006) (Figure 1). Compared to those with larger tumors, patients with HCC ≤ 3 cm had a significantly longer recurrence-free survival (12.0 [95% CI 10.7-13.3] vs. 9.7 [95% CI 8.2-11.2] months; p=0.02) and overall survival (52.5 [95% CI 45.5-59.4] vs. 34.7 [95% CI 30.7-38.7] months; p<0.0001). HCC size ≥ 3 cm, multifocality and AFP levels were independent predictors of extrahepatic recurrence.

Conclusion

Although the majority of patients treated with TACE do not develop metastases during their lifespan, knowledge of risk factors for extrahepatic recurrence (HCC size, multifocality, AFP levels) may help to assess patient prognosis and to identify patients deserving closer follow-up in order to start early systemic therapy.