Abstract HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic ...changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID‐19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct‐acting antiviral (DAA) era, and the COVID‐19 period, focusing on treatment outcomes (SVR12, non‐SVR12 and patients lost to follow‐up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal–Wallis test and chi‐square analysis, and were conducted adhering to the intention‐to‐treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow‐up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID‐19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high‐risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies.
Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of pre‐core HBV mutant (pre‐C mt) selection ...with virological/clinical outcomes in children followed‐up until adulthood. Eighty subjects (50‐M/30‐F), 70 HBeAg‐positive (87.5%), and 10 (12.5%) HBeAg‐negative/anti‐HBe‐positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2‐17) years, were followed‐up for 14.3 years (range: 1.1‐24.5); 46 (57.5%) received IFN treatment. HBV‐DNA and q‐HBsAg were tested by commercial assays, Pre‐Core 1896 mt by direct‐sequence, oligo‐hybridization‐assay, and allele‐specific‐PCR (sensitivity: 30%, 10%, and 0.1% of total viremia). HBeAg/anti‐HBe seroconversion (SC) occurred in 55/70 (78.6%) children. After SC, 8 (14.6%) developed HBeAg‐negative chronic hepatitis (CHB), 41 (74.5%) remain with HBeAg‐negative chronic infection, and 6 (10.9%) lost HBsAg. Baseline HBV‐DNA and HBsAg were lower in SC than in no‐SC children (median: 7.35 vs 8.95 Log IU/mL, P = 0.005, and 4.72 vs 5.04 Log IU/mL, P = 0.015). The prevalence of pre‐C mt increased rapidly (10‐40%) around SC. Eventually, pre‐C mt was detected in 100% of CHB, in 33% of chronic infections without disease, and in 16% of subjects who cleared HBsAg (P < 0.001). HBV‐DNA levels remained slightly higher in carriers of HBeAg negative infection with dominant/mixed pre‐C mt populations, than in those with dominant pre‐C wt (mean Log IU/mL: 3.83 and 3.42 vs 2.67, P = 0.007). In conclusion, pre‐C‐mt is selected during HBeAg/anti‐HBe SC in children with poor control of HBV replication, leading to HBeAg‐negative chronic‐active‐hepatitis during adulthood.
Background
Parenchyma-sparing liver surgery allows resecting hepatic veins (HV) at the hepatocaval confluence with minor (<3 adjacent segments) liver resections. PTFE graft can be used as a bridge to ...communicating-veins maturation to ensure the correct outflow of the spared liver. We present a video of an intrahepatic cholangiocarcinoma (IC) involving the three HV at the hepatocaval confluence treated with this approach.
Methods
In a 50-year old obese (BMI 44.8) male a 6-cm IC involving the hepatocaval confluence was identified during the follow-up for a kidney malignancy. At the preoperative CT scan the left HV was not detectable, the middle HV was incorporated within the tumor, and right HV had a 3-cm contact with the tumor. No communicating veins were evident at preoperative imaging.
Results
After a J-shape thoracophrenolaparotomy, the resection of segments II–III–IVa was partially extended to segment VIII–VII and I. The right HV was detached from the tumor, and the middle HV was reconstructed with a 7-mm ringed-armed PTFE graft anastomosed to V8. Surgery lasted 20 h and 55 min with an estimated blood loss of 3500 ml, but the postoperative course was uneventful and the patient was discharged on the 14th postoperative day. One month later the CT scan showed a patent PTFE graft with the maturation of communicating-veins. One year later a complete thrombosis of the PTFE graft was observed with normal liver perfusion and function, and the patient was disease-free.
Conclusions
PTFE-based parenchyma-sparing liver resection is a new tool to treat tumors located at the hepatocaval confluence exploiting the maturation of intrahepatic communicating-veins between main HV.
Major hepatectomy (MH) is often considered the only possible approach for colorectal liver metastasis (CRLM) at the hepato-caval confluence (CC), but it is associated with high morbidity and ...mortality. With the aim to reduce MH, we developed the "minor-but-complex" (MbC) technique, which consists in the resection of less than 3 adjacent liver segments with exposure of the CC and preservation of hepatic outflow until spontaneous maturation of peripheral intrahepatic shunts between main hepatic veins. We have evaluated applicability and outcome of MbC resections for the treatment of CRLM involving the CC. In this retrospective cohort study, all consecutive liver resections (LR) performed for CRLM located in segments 1, 7, 8, or 4a were classified as MINOR - removal of <3 adjacent segments; MbC - removal of <3 adjacent segments with CC exposure; and MH - removal of ≥ 3 adjacent segments. The rate of avoided MH was obtained by the difference between the rate of potentially MH (PMH) plus potentially inoperable cases and the rate of the MH performed. Taking into account that postoperative mortality is mainly related to the amount of resected liver, MbC was compared with minor resections for safety, complexity, and outcome. Of the 59 LR analyzed, 29 (49.1%) were deemed PMH and 4 (6.8%) potentially inoperable. Eventually, MH was performed only in 8 (13.5%) with a decrease rate of 42.4%. Minor LR was performed in 23 (39.0%) and MbC LR in 28 (47.5%) patients. Among MbC cases, 32.1% had previous liver treatments, 39.3% required vascular reconstruction (no reconstructed vessel thrombosis occurred before maturation of peripheral intrahepatic shunts between main hepatic veins), and 7.1% had grade IIIb-IV complications, their median hospital stay was 9 days and 90-day mortality was 0%. After a median follow-up of 22.2 months, oncological results were comparable with those of minor resections. MbC hepatectomy lowers the need for MH and allows for the resection of potentially inoperable patients without negative impact on safety and survival.
Background. R0 minor parenchyma-sparing hepatectomy (PSH) is feasible for colorectal liver metastases (CRLM) in contact with hepatic veins (HV) at hepatocaval confluence since HV can be ...reconstructed, but in the case of contact with the first-order glissonean pedicle (GP), major hepatectomy is mandatory. To pursue an R0 parenchyma-sparing policy, we proposed vessel-guided mesohepatectomy for liver partition (MLP) and eventually combination with liver augmentation techniques for staged major PSH. Methods. We analyzed 15 consecutive vessel-guided MLPs for CRLM at the hepatocaval confluence. Patients had a median of 11 (range: 0–67) lesions with a median diameter of 3.5 cm (range: 0.0–8.0), bilateral in 73% of cases. Results. Grade IIIb or more complications occurred in 13%, median hospital stay was 14 (range: 6–62) days, 90-day mortality was 0%. After a median follow-up of 17.5 months, 1-year OS and RFS were 92% and 62%. In nine (64%) patients, MLP was combined with portal vein embolization (PVE) or ALPPS to perform staged R0 major PSH. Future liver remnant (FLR) volume increased from a median of 15% (range: 7–20%) up to 41% (range: 37–69%). Super-selective PVE was performed in three (33%) patients and enhanced ALPPS (e-ALPPS) in six (66%). In two e-ALPPS an intermediate stage of deportalized liver PSH was necessary to achieve adequate FLR volume. Conclusions. Vessel-guided MLP may transform the liver in a paired organ. In selected cases of multiple bilobar CRLM, to guarantee oncological radicality (R0), major PSH is feasible combining advanced surgical parenchyma sparing with liver augmentation techniques when FLR volume is insufficient.
Summary Aims To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance. Methods Eighty HBV DNA-positive ...patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR). Results No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p < 0.05) and lower values of serum HBV DNA (1.77 × 106 ± 4.76 × 106 vs. 1.68 × 108 ± 5.46 × 108 ). In addition, a multivariate analysis identified the presence of a pre-existing HCV chronic infection as independently associated with severe acute hepatitis B ( p < 0.05). Conclusions HBV rtM204V/I lamivudine-resistant strains were detected in serum of 11 (13.7%) patients with acute hepatitis B by allele-specific polymerase chain reaction. The frequent association of rtM204V/I with a more severe acute hepatitis B and with a lower viral load may suggest that greater and/or more prolonged immune pressure might have induced their selection.
Abstract Background and aims Rapid virologic response is the best predictor of sustained virologic response with dual therapy in genotype-1 chronic hepatitis C, and its evaluation was proposed to ...tailor triple therapy in F0–F2 patients. Bio-mathematical modelling of viral dynamics during dual therapy has potentially higher accuracy than rapid virologic in the identification of patients who will eventually achieve sustained response. Study's objective was the cost-effectiveness analysis of a personalized therapy in naïve F0–F2 patients with chronic hepatitis C based on a bio-mathematical model (model-guided strategy) rather than on rapid virologic response (guideline-guided strategy). Methods A deterministic bio-mathematical model of the infected cell dynamics was validated in a cohort of 135 patients treated with dual therapy. A decision-analytic economic model was then developed to compare model-guided and guideline-guided strategies in the Italian setting. Results The outcomes of the cost-effectiveness analysis with model-guided and guideline-guided strategy were 19.1–19.4 and 18.9–19.3 quality-adjusted-life-years. Total per-patient lifetime costs were €25,200–€26,000 with model-guided strategy and €28,800–€29,900 with guideline-guided strategy. When comparing model-guided with guideline-guided strategy the former resulted more effective and less costly. Conclusions The adoption of the bio-mathematical predictive criterion has the potential to improve the cost-effectiveness of a personalized therapy for chronic hepatitis C, reserving triple therapy for those patients who really need it.
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