Summary
Background
Virus, host factors and their interplay influence Hepatitis B surface Antigen serum levels during Hepatitis B Virus (HBV) infection course and treatment.
Aim
To study the Pre‐S/S ...circulating quasispecies in a cohort of untreated, HBeAg negative, genotype‐D, HBsAg carriers.
Methods
We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV‐DNA ≤2000 IU/mL); 42 Grey Zone (GZ; HBV‐DNA ≤20 000 IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV‐DNA > 20 000 IU/mL). Population sequencing was applied to identify Pre‐S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M‐muts) on HBsAg.
Results
HBsAg serum levels were lower in ENI + GZ than in CH + CI (2.61 −1.10/4.06 vs 3.62 2.41/4.92 log10IU/mL, P < 0.001) and in CI than CH (3.48 2.41/4.38 vs 3.66 2.57/4.92 log10 IU/mL, P < 0.001). M‐muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P < 0.001) and mostly in Pre‐S2 (17.6%) than Pre‐S1 (5.8%) and Small‐S (10.8%; P < 0.001). Overall HBsAg serum levels were higher in carriers with M‐muts (3.56 0.95/4.38 vs 3.17 −1.10/4.92 log10 IU/mL, P < 0.001), but comparable in carriers with or without M‐mut when considering separately ENI + GZ (2.84 0.95/3.89 vs 2.61 −1.10/4.06 log10IU/mL, P = 0.330 and CH + CI (3.57 2.67/4.38 vs 3.63 2.41/4.92 log10IU/mL, P = 0.37). Infection phase (β: 0.422, P < 0.001), age (β: −0.260, P < 0.001), ALT (β: −0.103, P = 0.045), liver stiffness (β: −0.118, P = 0.039) and HBV‐DNA (β: 0.384, P < 0.001), but not M‐mut were independently associated with HBsAg serum levels.
Conclusions
In HBeAg negative, genotype‐D, carriers Pre‐S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV.
Background
Repeated hepatectomies in the therapeutic route of patients with colorectal liver metastases (CRLM) may improve their long term survival. Hepatic vein (HV) resection and reconstruction ...allows parenchyma-sparing hepatectomy (PSH) and R0 resections for CRLM in contact with one HV. We aimed at verifying the feasibility of PSH with double HV resection and direct reconstruction for CRLM in contact with two HVs at the hepatocaval confluence.
Methods
Out of 106 consecutive PSH performed for CRLM deep-located in segments I-IVa-VII-VIII, four (3.7%) PSH were performed with resection of CRLM en bloc with two adjacent HVs which were both reconstructed with double direct HV anastomosis: 3 cases between right-HV and middle-HV and 1 case between middle-HV and left-HV. Two patients had previously undergone liver resection. Three patients had one single lesion and one had 5 CRLMs.
Results
Median size of CRLMs in contact with HVs was 25 mm (range 22–30 mm). At histological examination, all resections were R0 except one R1-vascular (detachment from glissonean pedicle): in all cases at least one HV and in 1 case both HVs were infiltrated by the tumor cells. After median follow-up of 18 (range 3.5–41.2) months, all HVs were patent. All patients were alive and in good general conditions, and 3 patients were disease free (one of them following a liver re-resection). One patient experienced a grade IIIa complication. Median hospital-stay was 11 (range 9–13) days.
Conclusion
In patients with CRLMs involving two adjacent HVs at the hepatocaval confluence, liver resection with double HV resection and direct reconstruction is feasible and may be considered to guarantee oncological radicality (R0) and spare health parenchyma.
Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up.
We studied the association between ...hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)–negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy.
We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio HR, 1.576; P < .001) and a lower chance of HBsAg loss (HR, 0.454; P < .001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P < .001) and a lower chance of HBsAg loss (HR, 0.263; P < .001). A combination of both HBsAg <100 IU/mL and HBV DNA <100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg >100 IU/mL and HBV DNA >100 IU/mL (P < .001).
Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg <100 IU/mL with HBV DNA <100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.
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The current multicenter study shows that blood levels of hepatitis B virus DNA and hepatitis B surface antigen at 24 weeks after withdrawal of antiviral treatment can predict subsequent outcomes. These findings can be used to identify patients who may or may not require retreatment.
Liver magnetic resonance imaging (MRI) utilizing hepatocyte-specific contrast agent and diffusion-weighted imaging (DWI) is currently used to properly stage colorectal liver metastases (CRLM) in ...patients candidate to liver surgery. However, the added value of liver MRI in choosing the treatment strategy in resectable CRLM over computed tomography (CT)-scan is not clear.
This is a prospective monocentric collection of consecutive cases of patients with CRLM conceived with the aim to assess the added value of liver MRI in changing the initial treatment strategy planned according to CT-scan. Potential changes in the initially planned strategy were defined as: - from upfront surgery to perioperative chemotherapy (fluoropyrimidine and oxaliplatin) - from upfront surgery to first-line systemic therapy (doublet or triplet plus a biological agent) - from perioperative chemotherapy to first-line systemic therapy.
Hypothesising that MRI may induce a change in the choice of the treatment strategy in the 20% of cases (alternative hypothesis), against a null hypothesis of 5%, with one-tailed alpha and beta errors of 0.05 and 0.20 respectively, 27 patients were needed. The added value of liver MRI would have been considered clinically meaningful if at least 4 changes in the treatment strategy were observed.
Among 27 enrolled patients, upfront surgery and perioperative chemotherapy strategies were chosen in 17 (63%) and 10 (37%) cases, respectively, based on CT-scan. After liver MRI, additional liver lesions were found in 8 patients (30%) and the initial strategy was changed in 7 patients (26%) (4 initially deemed candidate to upfront surgery and 3 initially sent to perioperative chemotherapy) that were treated with first-line systemic therapy.
Our results support the indication of the current guidelines on the routine use of liver MRI in the initial workup of patients with resectable CRLM with an MRI-driven changes of initial treatment plan in a relevant percentage of cases.
•Initial hepatocyte-specific contrast-enhanced MRI and DWI may detect additional liver lesions than CTscan.•MRI causes change of the therapeutic plan established with CTscan alone in a relevant group of patients with resectable CRLM.•Liver MRI should be routinely used in the initial workup of patients with resectable CRLM.
