Journal of Clinical and Experimental Hepatology最新文献

The epidemiology of HCC is changing all over the world and the incidence of HCC is expected to continue increasing over the next 30 years. The changes are in the predisposing factors. Hepatitis B and hepatitis C as predisposing etiologies are decreasing while NAFLD/MAFLD is increasing. The increase in MAFLD is so great that despite the decrease in hepatitis B and C, the overall incidence of HCC is increasing. HCC in persons below the age of 20 years has distinct characteristics different from that of HCC in adults. The changing etiology of hepatocellular carcinoma has implications for the early detection, prevention, the stage of HCC at time of detection and in the treatment of HCC. The extent of these changes and their significance are discussed.

Background/Aims

Dengue-associated acute liver failure (ALF) poses a significant risk for mortality, especially in regions lacking access to liver transplantation. Although Plasma Exchange (PLEX) is recognized as a potential therapeutic intervention for dengue-associated ALF, data on its efficacy remain limited. This systematic review aimed to comprehensively examine the literature on PLEX and other combination therapies for dengue-associated ALF. It focused on assessing their effectiveness, safety profile, and potential implications for therapeutic interventions.

Methods

In this study, we conducted a systematic review to assess the efficacy and safety of PLEX and other combination therapies in patients with dengue-associated ALF. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria were used to search the PubMed, Scopus, Embase, Ovid, and Google Scholar databases. Studies published in English between 2019 and May 2024 were included. The titles and abstracts were reviewed for discrepancies, and any differences were resolved through discussion.

Results

Among the 713 studies assessed for review, 9 met the eligibility criteria. Studies have demonstrated that PLEX, both alone and in combination with other therapies, such as continuous renal replacement therapy (CRRT), improves liver function, survival rates, and neurological outcomes in patients with dengue virus. Both high- and low-volume plasma exchanges were effective.

Conclusion

This systematic review highlights the beneficial role of PLEX and the potential benefits of combination therapies in the treatment of rare and severe forms of dengue-associated ALF. However, given the limited sample sizes and the necessity for well-designed studies, further investigations are needed to determine the optimal volume of PLEX and the efficacy of additional therapeutic strategies.

Background and aim

Cytokeratin 19 (CK19)-positive HCC is a subtype of hepatocellular carcinoma (HCC) with poor biological behavior and resistance to different treatments including transarterial chemoembolization (TACE). The current study aimed to investigate the predictive value of serum CK 19 fragment 21-1 (CYFRA 21-1) and serum CK 19 fragment 2G2 (CK 19-2G2) for TACE response in patients with hepatitis C virus (HCV)-related HCC.

Methods

This prospective study assessed the pretreatment serum CYFRA 21-1 and CK 19-2G2 levels in 64 patients with HCV-related naïve HCC who underwent TACE to predict 1-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, 40 healthy individuals were included as controls. Pretreatment alpha-fetoprotein (AFP) was also measured for comparison.

Results

After exclusions, 60 patients completed TACE sessions, and the 1-year OS was 52%, and ORR post TACE was 71.8%. HCC patients with elevated levels of CYFRA 21-1, CK 19-2G2, or baseline AFP measuring ≥400 ng/ml have decreased 1-year OS and PFS after TACE. Serum CK19-2G2 was an independent predictor of 1-year OS using multivariate hazard regression analysis. Pretreatment normal serum CYFRA 21-1 levels (P = 0.047), serum AFP measuring <400 ng/ml (P = 0.016), and lower AST (P = 0.002) were independent predictors of ORR to TACE using multivariate logistic regression analysis. The predictive ability of pretreatment elevated serum CYFRA 21-1, AFP measuring ≥400 ng/ml, AFP + CYFRA 21-1, AFP + CK 19-2G2, or AFP + CYFRA 21-1+ CK19-2G2 to predict nonresponse (progressive disease) to TACE (area under the curve = 0.795, 0.690, 0.830, 0.725, and 0.850, respectively).

Conclusions

This study demonstrated that incorporating the measurement of serum CYFRA 21-1 or CK19-2G2 levels, along with AFP, during the initial diagnosis can aid in predicting poor 1-year OS, PFS, and ORR to TACE in patients with HCV-related HCC.

Background/Aims

In this study, we aim to develop a model for predicting gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI).

Methods

This study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination.

Results

A total of 40 CHB patients were enrolled and categorized into the high-risk group (n = 15) and the non-high-risk group (n = 25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%.

Conclusion

The prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

Background

The growth hormone-insulin-like growth factor (GH-IGF-1) axis and its impairment with sarcopenia, frailty, bone health, complications, and prognosis are not well characterized in cirrhosis.

Methods

We investigated the adult decompensated cirrhosis out-patients at a tertiary care institute between 2021 and 2023 for serum GH and IGF-1 levels, and associated them with sarcopenia (CT-SMI in cm²/m²), liver frailty index (LFI), osteodystrophy (DEXA), clinical decompensations (overall, ascites, encephalopathy, infection, and bleed), and survival up to 180 days.

Results

One-hundred-seventy-two patients, 95% males, aged 46.5 years (median). _logIGF-1 levels were negatively associated with sarcopenia, osteodystrophy, LFI, CTP, and MELD-Na score (P < 0.05 each). Patients with low IGF-1 levels had a higher incidence of complications (overall, ascites and encephalopathy) than those with intermediate, and high IGF-1 levels (P < 0.05 each). Both _logIGF-1 (AUC: 0.686) and MELD (AUC: 0.690) could predict 180-day mortality (P < 0.05, each). Adding _logIGF-1 with MELDNa further improved discriminative accuracy of MELDNa (AUC: 0.729) P < 0.001. The increase in IGF-1 on follow-up was associated with better survival and fewer complications.

Conclusion

Reduced IGF-1 levels reflect sarcopenia, frailty, and osteodystrophy in cirrhosis. Low IGF-1 are associated with severity, development of decompensations, and mortality.

Background

The current definition of lean is based on body mass index (BMI). However, BMI is an imperfect surrogate for adiposity and provides no information on central obesity (CO). Hence, we explored the differences in clinical profile and liver disease severity in lean patients with nonalcoholic fatty liver disease (NAFLD) with and without CO.

Methods

One hundred seventy lean patients with NAFLD (BMI <23 kg/m²) were divided into two groups depending upon the presence or absence of CO (waist circumference ≥80 cm in females and ≥90 cm in males). Noninvasive assessment of steatosis was done by ultrasound and controlled attenuation parameter (CAP), while fibrosis was assessed with FIB-4 and liver stiffness measurement (LSM). FibroScan-AST (FAST) score was used for non-invasive prediction of NASH with significant fibrosis.

Results

Of 170 patients with lean NAFLD, 96 (56.5%) had CO. Female gender (40.6% vs. 17.6%, P = 0.001), hypertriglyceridemia (58.3% vs. 39.2%, P = 0.01) and metabolic syndrome (23.9% vs. 4.1%, P < 0.001) were more common in the CO group. There was a poor correlation between BMI and waist circumference (r = 0.24, 95% CI: 0.09–0.38). Grade 2–3 steatosis on ultrasound was significantly more common in CO patients (30% vs. 12.3%, P = 0.007). CAP [312.5 (289.8–341) dB/m vs. 275 (248–305.1) dB/m, P = 0.002], FAST score [0.42 (0.15–0.66) vs. 0.26 (0.11–0.39), P = 0.04], FIB-4 and LSM were higher in those with CO. Advanced fibrosis was more prevalent among CO patients using FIB-4 (19.8% vs 8.1%, P = 0.03) and LSM (9.5% vs. 0, P = 0.04). CO was independently associated with advanced fibrosis after adjusting for BMI and metabolic risk factors (aOR: 3.11 (1.10–8.96), P = 0.03). Among these 170 patients, 142 fulfilled metabolic dysfunction associated steatotic liver disease (MASLD) criteria. CO was also an independent risk factor for advanced fibrosis in MASLD (3.32 (1.23–8.5), P = 0.02).

Conclusion

Lean patients with NAFLD or MASLD and CO have more severe liver disease compared to those without CO.

Hepatocellular carcinoma (HCC) represents a significant global health burden. Surgery remains a cornerstone in the curative treatment of HCC, and recent years have witnessed notable advancements aimed at refining surgical techniques and improving patient outcomes. This review presents a detailed examination of the recent innovations in HCC surgery, highlighting key developments in both surgical approaches and adjunctive therapies.

Advanced imaging technologies have revolutionized preoperative assessment, enabling precise tumour localization and delineation of vascular anatomy. The use of three-dimensional rendering has significantly augmented surgical planning, facilitating more accurate and margin-free resections. The advent of laparoscopic and robotic-assisted surgical techniques has ushered in an era of minimal access surgery, offering patients the benefits of shorter hospital stays and faster recovery times, while enabling equivalent oncological outcomes. Intraoperative innovations such as intraoperative ultrasound (IOUS) and fluorescence-guided surgery have emerged as valuable adjuncts, allowing real-time assessment of tumour extent and aiding in parenchyma preservation.

The integration of multimodal therapies, including neoadjuvant and adjuvant strategies, has allowed for ‘bio-selection’ and shown the potential to optimize patient outcomes. With the advent of augmented reality and artificial intelligence (AI), the future holds immense potential and may represent significant strides towards optimizing patient outcomes and refining the standard of care.

Background

Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored.

Methods

A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease.

Results

A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15–0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01–2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease.

Conclusions

Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

Hepatocellular carcinoma (HCC) carries significant morbidity and mortality. Management of the HCC requires a multidisciplinary approach. Surgical resection and liver transplantation are the gold standard options for the appropriate settings. Stereotactic body radiation therapy (SBRT) has emerged as a promising treatment modality in managing HCC; its use is more studied and well-established in advanced HCC (aHCC). Current clinical guidelines universally endorse SBRT as a viable alternative to radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), and transarterial radioembolisation (TARE), a recommendation substantiated by literature demonstrating comparable efficacy among these modalities. In early-stage HCC, SBRT primarily manages unresectable tumours unsuitable for ablative procedures such as microwave ablation and RFA. SBRT has been incorporated as a modality to downstage tumours or as a bridge to transplant. In the case of intermediate or advanced HCC, SBRT offers excellent results either as a single modality or adjunct to other locoregional modalities such as TACE/TARE. Recent data from late-stage HCC patients illustrate the effectiveness of SBRT in achieving local tumour control while minimising damage to surrounding healthy liver tissue. It has promising local control of approximately 80–90% in managing HCC. Additional prospective data comparing the efficacy of SBRT with the first-line recommended therapies such as RFA, TACE, and surgery are essential. The standard of care for patients with advanced/metastatic disease is systemic therapy (immunotherapy/tyrosine kinase inhibitors). SBRT, in combination with immune-checkpoint inhibitors, has an immune-modulatory effect that results in a synergistic effect. Recent findings indicate that the combination of immunotherapy and SBRT in HCC is well-tolerated and exhibits synergistic effects. Further exploration of diverse immunotherapy and radiotherapy strategies is essential to identify the appropriate time for combination treatments and to optimise dose and fraction regimens. Prospective, randomised studies are imperative to establish SBRT as the primary treatment for HCC.