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Summary: Background: Antiviral therapy for hepatitis C has the potential to improve liver function in patients with decompensated cirrhosis. Aims: To examine the virological response and effect of viral clearance in patients with decompensated hepatitis C cirrhosis all with MELD scores ≥15 following sofosbuvir/daclatasvir ± ribavirin. Methods: We prospectively collected data on patients who commenced sofosbuvir/daclatasvir for 24‐weeks under the Australian patient supply program (TOSCAR) and analysed outcomes including sustained viral response at 12 weeks (SVR12), death and transplant. Results: 108 patients (M/F, 79/29; median age 56years; Child‐Pugh 10; MELD 16; genotype 1/3, 55/47) received sofosbuvir/daclatasvir and two also received ribavirin. On intention‐to‐treat, the SVR12 rate was 70% (76/108). Seventy‐eight patients completed 24‐weeks therapy. SVR12 was achieved in 56 of these patients on per‐protocol‐analysis (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR12, median MELD and Child‐Pugh fell from 16(IQR15‐17) to 14(12‐17) and 10(9‐11) to 8(7‐9), respectively (P<.001). In those who died, MELD increased from 16 to 23 at death (P=.036). Patients who required transplantation had a significantly higher baseline MELD (20) compared to those patients completing treatment (16) (P=.0010). The odds ratio for transplant in patients with baseline MELD ≥20 was 13.8(95%CI 2.78‐69.04). Conclusions: SVR12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child‐Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post‐transplant. [ABSTRACT FROM AUTHOR]

Background Nucleos(t)ide analogues ( NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir ( ETV) and tenofovir disoproxil fumarate ( TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required. Aim To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus ( HBV)-monoinfected patients. Methods PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)). Results In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing 'real-world' clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations. Conclusions Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need. [ABSTRACT FROM AUTHOR]

Background Antepartum anti-viral therapy ( AVT) is often administered to prevent perinatal transmission of hepatitis B virus ( HBV) infection. Little is known about the effect of AVT on post-partum flare rates and severity. Aim To examine whether extending AVT beyond birth influences the post-partum course. Methods One hundred and one pregnancies in 91 women with HBV DNA levels ≥log 7 IU/ mL were included. AVT (initially lamivudine, later tenofovir disoproxil fumarate) was commenced from 32 weeks gestation and stopped soon after birth and at 12 weeks post-partum. Outcomes according to post-partum treatment duration were examined: Group 1 = AVT ≤4 weeks ( n = 44), Group 2 = AVT >4 weeks ( n = 43), Group 3 = no AVT ( n = 14). Results The majority of women were HBeAg+ (97%), median age 29 years, baseline HBV DNA log 8.0 IU/ mL and follow-up 48 weeks post-partum. Post-partum treatment duration was 2 weeks for Group 1 and 12 weeks for Group 2, P < 0.01. Flare rates were not significantly different: Group 1 = 22/44 (50%), Group 2 = 17/43 (40%) and Group 3 = 4/14 (29%), P = 0.32. Onset of flare was similar at 8/10/9 weeks post-partum for Groups 1/2/3 respectively, P = 0.34. The majority of flares spontaneously resolved. HBeAg seroconversion ( n = 1/5/1 in Groups 1/2/3, P = 0.27) was not associated with treatment duration or the occurrence of a post-partum flare. Conclusions Post-partum flares are common and usually arise early after delivery. They are often mild in severity and most spontaneously resolve. Extending anti-viral therapy does not protect against post-partum flares or affect HBeAg seroconversion rates. [ABSTRACT FROM AUTHOR]

Background Hyponatraemia in liver failure is associated with increased morbidity and mortality. Improving serum sodium in liver failure has been observed in patients receiving terlipressin. Methods We assessed the response of hyponatraemia in patients with liver failure to terlipressin using comparative retrospective analysis. Results Twenty-three patients received terlipressin for hyponatraemia after failed conservative management (median age 52 years (27-67), model for end-stage liver disease score 28 (16-38)). The median therapy was 7 days (1-27), with an average total dose of 25 mg (4-90) and a mean follow up of 51 days (5-1248). These patients were compared with 11 hyponatraemic patients managed conservatively during the same period with comparable age, baseline serum sodium and follow up. After 1 week of terlipressin therapy, serum sodium increased from a median of 120 (115-128) to 129 mmol/ L (121-144) ( P < 0.001), and at the end of terlipressin therapy, the serum sodium had increased significantly to 131 mmol/ L (120-148) ( P < 0.001). In comparison, in the conservatively managed group, the serum sodium did not increase significantly from the baseline of 123 (117-127) mmol/ L. Adverse events occurred in 26% of patients receiving terlipressin, which predominantly pulmonary oedema. Importantly, more hyponatraemic patients treated with terlipressin (48%) were alive compared with the conservative group (18%), despite the latter having a significantly lower baseline median MELD score of 21 (16-30) ( P = 0.008). Moreover, the transplant-free survival was higher in the terlipressin (30%) compared with the conservative group (0%). Conclusions Terlipressin is effective in treating hyponatraemia in liver failure. Importantly, terlipressin use results in better transplant-free survival but also more adverse events. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the demand for liver transplantation (LTx) and patient outcomes on the waiting list at the Australian National Liver Transplantation Unit, Sydney over the last 20 years. Methods: We performed a retrospective analysis with the data divided into three eras: 1985-1993, 1994-2000 and 2001-2008. Results: The number of patients accepted for LTx increased from 320 to 372 and 548 ( P < 0.001) with the number of LTx being performed increasing from 262 to 312 and 452 respectively ( P < 0.001). The median adult recipient age increased from 45 to 48 and 52 years ( P < 0.001) while it decreased in children from 4 to 2 and 1 years respectively ( P= 0.001). In parallel, the deceased donor offers decreased from 1003 to 720 and 717 ( P < 0.001). Methods to improve access to donor livers have been used with the use of split livers, extended criteria and non-heart beating donors, resulting in increased acceptance of deceased donor offers by 65% and 115% in the second and third eras when compared with the first era ( P < 0.001). However, the adult median waiting time has increased from 23 to 41 and 120 days respectively ( P < 0.001). This was associated with increased adult mortality on the waiting list from 23 to 40 and 122 respectively ( P < 0.001). Conclusions: Despite the increasing proportion of donor offers being used, the waiting list mortality is increasing. A solution to this problem is an increase in organ donation to keep pace with the escalating demand for LTx. [ABSTRACT FROM AUTHOR]

Background: To investigate endothelin-1 (ET-1)-dependent hepatic and mesenteric vasoconstriction, and oxygen and lactate fluxes in an acute, fixed low cardiac output (CO) state. Methods: Sixteen anesthetized, mechanically ventilated pigs were studied. Cardiac tamponade was established to reduce portal venous blood flow (QPV) to 2/3 of the baseline value. CO, hepatic artery blood flow (QHA), QPV, hepatic laser-Doppler flow (LDF), hepatic venous and portal pressure, and hepatic and mesenteric oxygen and lactate fluxes were measured. Hepatic arterial (RHA), portal (RHP) and mesenteric (Rmes) vascular resistances were calculated. The combined ETA–ETB receptor antagonist tezosentan (RO 61-0612) or normal saline vehicle was infused in the low CO state. Measurements were made at baseline, after 30, 60, 90 min of tamponade, and 30, 60, 90 min following the infusion of tesozentan at 1 mg/kg/h. Results: Tamponade decreased CO, QPV, QHA, LDF, hepatic and mesenteric oxygen delivery, while hepatic and mesenteric oxygen extraction and lactate release increased. RHA, RHP and Rmes all increased. Ninety minutes after tesozentan, QPV, LDF and hepatic and mesenteric oxygen delivery and extraction increased approaching baseline values, but no effect was seen on CO or QHA. Hepatic and mesenteric handling of lactate converted to extraction. RHA, RHP and Rmes returned to baseline values. No changes were observed in these variables among control animals not receiving tesozentan. Conclusion: In a porcine model of acute splanchnic hypoperfusion, unselective ET-1 blockade restored hepatomesenteric perfusion and reversed lactate metabolism. These observations might be relevant when considering liver protection in low CO states. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 43-year-old man for lumen-apposing metal stent (LAMS) removal with a medical history of alcoholic liver disease and pancreatitis.

In 2015, there are a few absolute contraindications to liver transplantation. In adult patients, survival post-liver transplant is excellent, with 1-year survival rate >90% and 5-year survival rates >80% and predicted median allograft survival beyond 20 years. Patients with a Child-Turcotte Pugh score ≥9 or a model for end-stage liver disease ( MELD) score >15 should be referred for liver transplantation, with patients who have a MELD score >17 showing a 1-year survival benefit with liver transplantation. A careful selection of hepatocellular cancer patients results in excellent outcomes, while consideration of extra-hepatic disease (reversible vs irreversible) and social support structures are crucial to patient assessment. Alcoholic liver disease remains a challenge, and the potential to cure hepatitis C virus infection together with the emerging issue of non-alcoholic fatty liver disease-associated chronic liver failure will change the landscape of the who in the years ahead. The when will continue to be determined largely by the severity of liver disease based on the MELD score for the foreseeable future. [ABSTRACT FROM AUTHOR]

A response from the authors of the article ``Terlipressin Therapy for Moderate to Severe Hyponatraemia in Patients with Liver Failure'' in the March 2013 issue is presented.

Background: Low birthweight (LBW), infants weighing less than 2,500 g, is a global health concern associated with high infant morbidity and mortality rates. This study investigates LBW prevalence and its relation to maternal sociodemographic characteristics and lifestyle behaviors factors in the United States (US)., Methods: This analysis used the National Survey of Children's Health (NSCH) data from 2016 to 2021, including n = 225,443 children aged 0-17 years. 18,131 had LBW (<2,500 g), and 2810 had very LBW (VLBW) (<1,500 g). Logistic regression calculated odds ratios (OR) using LBW as the dependent variable, adjusting for various factors., Results: Between 2016 and 2021 in the United States, LBW prevalence averaged 9.31%, with VLBW at 1.50%. Mothers aged 18-35, White, had the lowest LBW (7.63%) and VLBW (1.17%) rates. Mothers aged ≤18 years, black, had the highest LBW (15.45%) and VLBW infants (4.70%). Maternal age emerged as a significant LBW factor, with an OR of 1.27 for ≤18 and 1.19 for >35. Children in poor health had the highest OR (2.87). Race/ethnicity and other disparities were observed., Conclusion: Our study highlights LBW risk among non-White mothers with specific criteria, emphasizing the need for continued exploration of intersectional targets for change that are exacerbating LBW disparities among marginalized populations which may be artificially attributed to biologic determinants and individual-level risk factors. In-depth analysis of repressive structures at the root of inequalities demand continued research on macro levels of influence. Customized healthcare reform holds the greatest potential to disrupt the patterns contributing to poor health outcomes among LBW children, and will ultimately maximize the reach and effectiveness of health promotion strategies and clinical practices aimed to improve universal maternal and infant health., (© 2023 Wiley Periodicals LLC.)

Background: Antiviral therapy for hepatitis C has the potential to improve liver function in patients with decompensated cirrhosis., Aims: To examine the virological response and effect of viral clearance in patients with decompensated hepatitis C cirrhosis all with MELD scores ≥15 following sofosbuvir/daclatasvir ± ribavirin., Methods: We prospectively collected data on patients who commenced sofosbuvir/daclatasvir for 24-weeks under the Australian patient supply program (TOSCAR) and analysed outcomes including sustained viral response at 12 weeks (SVR12), death and transplant., Results: 108 patients (M/F, 79/29; median age 56years; Child-Pugh 10; MELD 16; genotype 1/3, 55/47) received sofosbuvir/daclatasvir and two also received ribavirin. On intention-to-treat, the SVR12 rate was 70% (76/108). Seventy-eight patients completed 24-weeks therapy. SVR12 was achieved in 56 of these patients on per-protocol-analysis (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients failed to complete therapy. In patients achieving SVR12, median MELD and Child-Pugh fell from 16(IQR15-17) to 14(12-17) and 10(9-11) to 8(7-9), respectively (P<.001). In those who died, MELD increased from 16 to 23 at death (P=.036). Patients who required transplantation had a significantly higher baseline MELD (20) compared to those patients completing treatment (16) (P=.0010). The odds ratio for transplant in patients with baseline MELD ≥20 was 13.8(95%CI 2.78-69.04)., Conclusions: SVR12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child-Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post-transplant., (© 2017 John Wiley & Sons Ltd.)

Background: Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study., Methods: A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily., Results: Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma., Conclusions: Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy., Aim: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks., Methods: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72., Results: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log 10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72., Conclusions: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72., (© 2016 John Wiley & Sons Ltd.)