HCV-related Decompensated Cirrhosis Research Articles

Trends in viral hepatitis liver-related morbidity and mortality in New South Wales, Australia

Monitoring hepatitis B virus (HBV) and hepatitis C virus (HCV) liver-related morbidity and mortality is key to evaluate progress towards elimination targets. HBV and HCV notifications in NSW, Australia (1995-2022) were linked to hospital and mortality records. Temporal trends in decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and mortality were evaluated among people notified for HBV and HCV. Segmented Poisson regression models were used to assess the impact of the viral hepatitis elimination era (1 January 2015-31 December 2022) on advanced liver disease and mortality. During 1995-2022, there were 64,865 people with an HBV notification and 112,277 people with an HCV notification in NSW. Between 2002 and 2022, there were significant reductions in age-adjusted HBV- and HCV-related DC, HCC, and liver-related mortality. Among those with HBV, age-standardised incidence per 1000 person-years (py) in 2002, 2015, and 2022 was 3.08, 1.47, and 1.16 for DC (p<0.001); 2.97, 1.45, and 0.75 for HCC (p<0.001); and 2.84, 1.93, and 1.40 for liver-related mortality (p<0.001). Among those with HCV, age-standardised incidence per 1000 py in 2002, 2015, and 2022, was 5.53, 4.57, and 2.31 for DC (p<0.001); 2.22, 2.59, and 1.87 for HCC (p<0.001); and 3.89, 4.73, and 3.16 for liver-related mortality (p<0.001). In 2022, absolute liver-related mortality per 100,000 population was 0.95 for HBV and 3.56 for HCV. In adjusted analyses, older age, comorbidity, and a history of alcohol use disorder were associated with increased liver-related mortality among those with HBV and HCV. This population-level study demonstrated declining risks of DC, HCC, and mortality, with HBV-related declines commencing well before elimination era while HCV-related declines were mostly during elimination era. Population liver mortality indicates elimination target achieved for combined viral hepatitis and HBV, but not HCV. The Kirby Institute, UNSW Sydney, and New South Wales Ministry of Health, Australia.

Recompensation of Chronic Hepatitis C-related decompensated cirrhosis following direct-acting antiviral therapy: Prospective Cohort study from an HCV elimination program.

Background and AimsChronic hepatitis C(CHC) related decompensated cirrhosis is associated with lower SVR-12 rates and variable regression of disease severity following direct-acting antiviral agents (DAAs). We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. MethodsBetween July 2018-July 2023, patients with decompensated CHC-related cirrhosis post DAAs treatment, were evaluated for SVR-12 and then had 6-monthly follow-up. ResultsOf 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2±11.5 years,63% men, MELD-Na:16.5± 4.6,87% genotype 3) were enrolled. SVR-12 was 81.8% after one course; ultimately SVR was 90.8% following additional treatment. Decompensation events included ascites (1098,95.3%), hepatic encephalopathy (191,16.6%), and variceal bleeding (284,24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284(24.7%) at a median time of 16.5(IQR-14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin(aHR-0.6,95%CI-0.5-0.8,P<0.001), INR(aHR-0.2,95%CI:0.1-0.3,P<0.001), absence of large esophageal varices(aHR-0.4,95%CI:0.2-0.9,P=0.048), or gastric varices (aHR-0.5,95%CI:0.3-0.7,P=0.022) predicted recompensation. Portal hypertension (PHT) progressed in 158(13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR-1.6,95%CI:1.2-2.8, P=0.042), and presence of large varices (aHR-2.9,95%CI:1.3-6.5,P<0.001) were associated with PHT progression. Further decompensation was seen in 221(19%);145 patients died and 6 underwent liver transplant. A decrease in MELDNa of ≥3 was in 409(35.5%) and a final MELDNa score of <10 was in 335(29%), but 2.9% developed HCC despite SVR-12. ConclusionsSVR-12 in HCV-related decompensated cirrhosis in a predominant genotype 3 population, led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and HCC developed in 2.9% of patients.

Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

BackgroundIn HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort.MethodsWe identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits.Results559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17–0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06–0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05–0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29–0.93, p = 0.03).ConclusionTreatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis.Trial registration: ClinicalTrials.gov registry number: NCT01953458.

Sofosbuvir-based antiviral therapy provided highly treatment efficacy, safety, and good tolerability for Taiwanese chronic hepatitis C patients with decompensated cirrhosis.

For patients with hepatitis C virus (HCV)-related decompensated cirrhosis, poor prognosis was documented due to the development of portal hypertension-related complications and hepatocellular carcinoma. Sofosbuvir-based direct-acting antiviral agents (DAAs) has revolutionized the treatment landscape of HCV, particularly in this subpopulation. To date, real-world efficacy, tolerability, and safety profiles for Taiwanese HCV-related decompensated cirrhosis treated by DAAs have not been reported. Between December 2015 and June 2020, 50 consecutive HCV-related Child-Turcotte-Pugh (CTP) classes B or C cirrhotics treated by sofosbuvir-based DAAs (with daclatasvir: 7, with ledipasvir: 32, with velpatasvir: 10, with ledipasvir then shifted to velpatasvir: 1) were enrolled. Forty-seven (94%) patients used DAAs in combination with low-dose ribavirin. SVR12 was defined by undetectable HCV RNA (<15 IU/mL) at treatment end and 12 weeks after the completion of therapy. The mean age of the enrolled patients was 68.1 ± 11.2 years, 18% of the patients were CTP class C, and the baseline HCV RNA level was 5.42 ± 1.2 log10 IU/mL. The genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with an unclassified HCV genotype. After DAAs treatment, the rates of undetectable HCV RNA at week 4 and at the end of the treatment were 88.9% and 98.0%, respectively. Subjective adverse events were reported by 42.0% of the patients, but they were generally mild and could be relieved by medications. One patient did not finish therapy due to sepsis with multiple organ dysfunction. The overall SVR12 rate was 96.0% (CTP class B: 97.6%, CTP class C: 88.9%). A significant improvement in hepatic functional reserve was noted after successful antiviral therapy. For patients with HCV-related decompensated cirrhosis, which has been considered a contraindication for interferon-based therapy, sofosbuvir-based all-oral DAAs provided high treatment efficacy, acceptable safety, and good tolerability.

Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis.

Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy. We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response. A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment. In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12. DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.

A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement

To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p= 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

Real‐world efficacy of sofosbuvir plus velpatasvir therapy for patients with hepatitis C virus‐related decompensated cirrhosis

Combination therapy with sofosbuvir (SOF) plus velpatasvir (VEL) is approved for patients with hepatitis C virus (HCV)-related decompensated cirrhosis. We analyzed the real-world efficacy of SOF/VEL therapy. Thirty-three patients with HCV-related decompensated cirrhosis (25 and eight patients with Child B and C, respectively) were treated with SOF/VEL for 12weeks. The HCV non-structural protein (NS)5A and NS5B drug resistance-associated substitutions (RASs) were determined by direct sequencing. Thirty-two of 33 patients completed the treatment, but the remaining patient discontinued the therapy during third week of the treatment due to aggravation of hepatic encephalopathy. Serum HCV-RNA became negative during the treatment in all patients but relapsed after the end of therapy in five patients. In total, 28 out of 33 patients (85%) achieved sustained virological response 12weeks following completion of treatment (SVR12). The SVR12 rate was 96% in patients with Child B, but significantly lower, at 50%, in patients with Child C (P < 0.05). In genotype 1b HCV-infected patients, all eight patients without baseline NS5A RASs, but only three of seven patients with RASs, achieved SVR12. Multivariate analysis identified Child B (odds ratio, 35.8 for Child C; P = 0.045) as an independent predictor of SVR12. Median serum albumin levels significantly increased only in patients who achieved SVR12. Child-Pugh scores improved in 16 of 28 patients (57%) following achievement of SVR12. The effect of SOF/VEL therapy is lower for patients with Child C. Improvement of hepatic function is expected after viral eradication with SOF/VEL therapy in patients with decompensated cirrhosis.

DAA therapy and long-term hepatic function in advanced/decompensated cirrhosis: Real-world experience from HCV-TARGET cohort

Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. Patients with advanced/decompensated cirrhosis (model for end-stage liver disease [MELD] ≥10), in whom NS5A-containing DAA therapy was initiated prior to September 2018, were included (from the HCV-TARGET cohort). Treatment outcomes and the impact of treatment on short-term and long-term hepatic function were examined. A total of 642 patients were analyzed. The mean age was 60 years, 68% were male. The median baseline MELD was 12 (range 10-39) and 64% had prior decompensation. Among patients with available virologic outcomes, 90.5% achieved a sustained virologic response at 12 weeks (SVR12). Eighty (24%) patients achieved a clinically significant decrease in MELD by ≥3 points during short-term follow-up (9-26 weeks after the end of treatment). However, in long-term follow-up (median of 4 years after treatment), mean changes in MELD (-0.30 points), total bilirubin (+0.23 mg/dl) and albumin (+0.36 g/dl) were marginal. Fifty-one patients died and 22 underwent liver transplant. In long-term follow-up, a clinically meaningful decrease in MELD of ≥3 occurred in 29% and a final MELD score of <10 was achieved in 25%. In a large real-world experience of patients with advanced/decompensated HCV-related cirrhosis treated with DAAs, there were only marginal improvements in MELD, total bilirubin, or albumin at long-term follow-up (after achieving SVR12). These patients may remain at high risk of decompensation and must continue to be closely monitored. CLINICALTRIALS.GOV: NCT01474811. Hepatitis C virus infection can now be cured with medications, even in patients who have advanced scarring of the liver (cirrhosis). In this study, we evaluated whether liver function improves or deteriorates in the long-term, following successful treatment of hepatitis C in patients with cirrhosis. We found that overall liver function was relatively stable with only 29% of patients achieving a clinically meaningful improvement in liver function, and we therefore believe that these patients require ongoing monitoring.

Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study

ObjectivePopulation-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis...

Tolerance and Effectiveness of Oral Direct Acting Antivirals in Treatment of HCV Egyptian patients with Decompensated Liver Cirrhosis

Background: Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efficacy and safety of DAAs in the management of HCV-related decompensated cirrhosis. Objective: The current study aimed to evaluate the efficacy and safety of DAAs in managing HCV patients with decompensated cirrhosis and the impact of achieving sustained virological response on improving the quality of life, short term survival and if viral eradication would step down CTP score. Patients and Methods: The study included a treatment group I (n = 25) composed of HCV patients with decompensated cirrhosis Child B and group II (n = 22) with decompensated cirrhosis Child C. both groups received DAAs (sofosbuvir 400 mg, daclatasvir 60 mg) plus ribavirin as tolerated for 3 months and follow-up was done for 6 months. Results: In both treated groups, there were improvements in platelet count, albumin, Child-Torcout-Pugh (CTP) (p = 0.001) and a significant reduction in the frequency of hepatic encephalopathy (HE). Also, there was improvement in quality of life of both treated groups. Conclusion: Treatment of HCV with decompensated cirrhosis with DAAS had improved CTP score, quality of life and survival.

Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia

Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001-2014) and DAA therapy (2015-2017) eras in New South Wales, Australia. HCV notifications (1993-2016) were linked to hospital admissions (2001-2017) and mortality (1995-2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively. Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04-1.05], 1.08 [95% CI 1.07-1.08], 1.07 [95% CI 1.06-1.07], and 1.05 [95% CI 1.04-1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95-0.99] and 0.96 [95% CI 0.94-0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97-1.03] and 1.01 [95% CI 1.00-1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14-3.58). In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities. Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C.

Management of HCV-related decompensated cirrhosis with direct-acting antiviral agents: who should be treated?

Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efficacy and safety of DAAs in the management of HCV genotype 4-related decompensated cirrhosis. The study included a treatment group (n = 160) composed of HCV patients with decompensated cirrhosis who received DAAs for 3months and a matched control group (n = 80) who preferred not to receive DAAs, follow-up was for 24-31months. In treatment group; there were improvements in platelet count, albumin, CTP (p = 0.001) and MELD scores (p = 0.03), a significant reduction in the frequency of hepatic encephalopathy (HE). SVR was achieved in 90%. Hepatocellular carcinoma (HCC) developed in 10% (n = 18) within 6.8 ± 2.5months after DAAs, survival was higher in the treated vs. the control group (28.9 ± 0.95 vs. 11.4 ± 2.2months, p = 0.001). Liver volume by ultrasound at a cutoff 495ml was predictive of complications after DAAs therapy mainly HCC and reduced survival with sensitivity 93.2%, specificity 72%. HCV with decompensated cirrhosis and adequate liver volume had a 90% SVR with improved CTP&MELD and survival. (NCT03547895).

Treatment with direct-acting antivirals improves the clinical outcome in patients with HCV-related decompensated cirrhosis: results from an Italian real-life cohort (Liver Network Activity-LINA cohort).

Direct-acting antivirals (DAAs) are safe and effective for the treatment of HCV infection. However, data regarding their efficacy in patients with Child-Pugh B cirrhosis are scarce and their capability in improving liver function is debated. The aim of our study was to assess the clinical benefits of treatment with DAA in subjects with Child-Pugh B cirrhosis. We conducted a prospective multicentre study among patients with Child-Pugh B cirrhosis of an Italian real-life HCV cohort (LINA cohort) who received treatment with DAAs. Among 89 patients enrolled, the rate of sustained virologic response 12 was 95.5%. No discontinuation occurred, no patient died during treatment. Most patients had Genotype 1 (1b 61.8%, 1a 11.2%). Conversely, 22.5%, 1.1% and 3.4% of patients had Genotype 2, 3 and 4, respectively. At last observation, 61.8% of patients switched to a Class A cirrhosis, 33.7% remained in Class B and 4.5 worsened to Child C (p < 0.001). Liver parameters significantly improved from baseline to 12weeks after the end of treatment. Previous anti-HCV treatments and the presence of decompensated cirrhosis at 1month of treatment were significantly associated with a decompensated cirrhosis at the last observation. Treatment with DAA in patients with Child-Pugh B cirrhosis is safe and leads to a very high rate of viral clearance, a significant rate of re-compensation and an improvement in liver function. Further studies are needed to assess the impact of treatment on survival and quality of life in long-term follow-up.

63. Partial splenic artery embolization therapy in hemophilia a with decompensated cld causing hypersplenism: caution to hepatologists- a case report

Background and Aims: Partial splenic artey embolization (PSE) have been prescribed extensively by hepatologists to avoid splenectomy in special case of hemophilia A and to improve symptoms and hematological indices, and to also decrease CLD decompensation. Splenomegaly is a common sequela of cirrhosis, and is frequently associated with decreased hematologic indices including pancytopenia. In liver tissues after PSE, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were remarkably increased, speculating that PSE induced liver regenerative response and regularly monitoring of symptoms are required. Case Summary: A 41 Year old, male known case of Hemophilia A with decompensated cirrhosis with portal hypertension with hypersplenism (pancytopenia) secondary to hepatitis C [MELD Na-12, CTP-9/B] presented with 3 month history of dyspnoea of exertion (DOE) with malena with progressive developement oedema in both lower extremities and abdominal distention, requiring support while walking. On further evaluation, normal renal function, hypoalbuminemia and first time detected as anti HCV POSITIVE and found to have elevated HCV RNA load 145000, with genotype 3, factor VIII assay <15 obtained. Patient was diagnosed with HCV related decompensated cirrhosis of liver with portal hypertension induced hypersplenism. After patient underwent partial splenic artery embolization, patient's symptoms improved and he had decreased ascites and pedal edema and improved hematological indices over a period of a 3 month. Conclusions: Partial splenic artery embolization has a great potential in the management of hypersplenism due to liver cirrhosis. Partial splenic artery embolization is particularly valuable amongst those cirrhotic patients who are not viable candidates for splenectomy in special case like hemophilia A. The author has none to declare.

The contribution of alcohol use disorder to decompensated cirrhosis among people with hepatitis C: An international study

The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

The future of liver transplantation for viral hepatitis.

In hepatitis C virus (HCV)-infected patients, transplantation can be justified by decompensated cirrhosis, hepatocellular carcinoma (HCC) or both. During the last decade, HCV infection accounted for about 30% of the indications for transplantation in Europe and North America. Direct antiviral agents (DAAs) are highly effective at curing HCV, even in patients with end-stage cirrhosis. In the future, the incidence of HCV-related decompensated cirrhosis will continue to decrease. The incidence of HCC will also decrease, but a large cohort of patients with cirrhosis will still be at risk of developing HCC even after HCV has been cured. They will continue to represent potential candidates for transplantation. Overall, HCV will account for a significantly lower proportion of indications for transplantation in the future. However, generalization of DAAs is unlikely to affect the total transplantation volume as the gap between donors and potential recipients markedly exceeds 30%. In addition, non-alcoholic steatohepatitis (NASH) is a rapidly growing indication for transplantation. The high barrier to resistance nucleos(t)ide analogues (NUCs) have been used for several years to treat hepatitis B virus (HBV) infection. Decompensated HBV cirrhosis now represents a very uncommon indication for transplantation. HCC remains the leading indication in HBV-infected patients awaiting transplantation. NUCs plus anti-HBs immune globulins or NUCs alone are highly effective at preventing post-transplant HBV recurrence. However, continuous prophylaxis is still needed as extrahepatic HBV particles persist with a potential for recurrence. Post-transplant immunosuppression facilitates recurrence. In the future, an important challenge will be to cure HBV by eliminating residual HBV particles.

Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial

Hepatitis C virus (HCV) treatment regimens with direct-acting antivirals have not been extensively studied in patients with decompensated cirrhosis. We assessed patient-reported outcomes (PROs) in patients with decompensated cirrhosis given a fixed-dose combination of sofosbuvir and velpatasvir with and without ribavirin. This study was an exploratory analysis of data collected in a randomised, open-label phase 3 trial (ASTRAL-4) in which patients with HCV-related decompensated cirrhosis were randomly assigned to an all-oral fixed-dose combination of sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks, sofosbuvir and velpatasvir plus oral ribavirin (weight-based 1000 mg or 1200 mg) for 12 weeks, or sofosbuvir and velpatasvir for 24 weeks. Eligible patients were aged 18 years or older with any HCV genotype and decompensated cirrhosis at screening. PROs were collected for the intention-to-treat population using four questionnaires, Short Form (36) Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), the Chronic Liver Disease Questionnaire-HCV Version (CLDQ-HCV), and the Work Productivity Activity Index:HCV (WPAI), which were given prospectively to patients before, during, and after treatment. The ASTRAL-4 study is registered with ClinicalTrials.gov, number NCT02201901. Patients were enrolled at 47 hepatology outpatient practices in the USA from Aug 19, 2014, to Dec 19, 2014. 267 patients with HCV-related decompensated cirrhosis were included. In patients given sofosbuvir and velpatasvir for 12 weeks (n=90), clinically significant improvements in PROs started 4 weeks after treatment initiation (+4·4 to +7·5 points on a 0-100 scale at treatment week 4). By the end of treatment, mean improvements in PROs of +5·3 to +16·0 points were noted in all PROs except for role emotional, mental component summary, and social wellbeing scores and work productivity metrics by WPAI:HCV. Similar end-of-treatment improvements (+3·8 to +17·0 points) were observed in patients given sofosbuvir and velpatasvir for 24 weeks (n=90). In patients given sofosbuvir and velpatasvir plus ribavirin (n=87), PRO scores decreased within 4 weeks of treatment (-3·6 to -6·9 points), although scores returned to the baseline levels by the end of treatment. After treatment cessation, significant improvements in all PROs were similar between the treatment groups (all p>0·01) and, by post-treatment week 24, improvements were between +4·9 and +21·2 points. In multivariate analysis, predictors of PRO impairment were treatment naivety, anxiety, use of anxiolytics, use of antidepressants, use of opioids, ribavirin use, the presence of ascites, encephalopathy, insomnia, and depression. A clinically significant early (within 4 weeks) and sustained improvement in PROs was observed in patients with HCV-related decompensated cirrhosis who were given sofosbuvir and velpatasvir without ribavirin. A similar regimen with ribavirin resulted in a temporary decrease in PROs, which completely resolved after 8 weeks of treatment. Accompanied by high efficacy, the favourable effect of treatment on PROs improves patients' experience in this difficult-to-treat population with HCV. Gilead Sciences.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Patients with Decompensated Cirrhosis

HCV-related decompensated liver cirrhosis is a life-threatening illness with an average 5-year survival rate of 50%. Because these patients have higher risk of morbidity and mortality including development of hepatocellular carcinoma, the benefits of eradicating the virus may be greater than in those with less-advanced disease. Recently, direct-acting antiviral agents (DAAs) are replacing interferon-based regimens that have serious adverse events and low tolerability in the treatment of HCV infection. Many clinical trials using combination of several DAAs with or without ribavirin are now actively on-going in HCV-related decompensated cirrhosis, and encouraging data are beginning to appear. In this review, recent advances in the treatment of HCV-related decompensated cirrhosis are introduced with special focus on new DAAs.

Resource Utilization and Direct Medical Costs of Chronic Hepatitis C in Thailand: A Heavy but Manageable Economic Burden

ObjectiveTo estimate the cost for the management of chronic hepatitis C (CHC) and related morbidities by using a payer perspective in Thailand. MethodsData elements were extracted from medical records of 542 patients newly diagnosed with CHC in five tertiary care hospitals across Thailand. All patients were divided into five health states: noncirrhotic CHC, hepatitis C virus (HCV)-related compensated cirrhosis, HCV-related decompensated cirrhosis, HCV-related hepatocellular carcinoma, and HCV-related liver transplantation. Resource utilization data for each patient during a 12-month follow-up study period were compiled, and reference prices published by the Thai government were used to estimate the cost for each health state. The average cost was calculated and categorized into various groups, for example, laboratory and diagnostic tests, procedures, medication, and hospitalization. ResultsThe average number of outpatient visits per patient was approximately six visits in all cohorts. The HCV-related hepatocellular carcinoma and liver transplantation cohorts had a higher average number of inpatient admissions per patient. The average number of days per admission varied from fewer than 3 days to 1 week or more across all the health states. The average annual total cost per patient varied across all health states from approximately 170,000 to 600,000 baht, and medication cost was the largest portion in every cohort, except the HCV-related liver transplantation cohort in year 1. Among all medications, the average annual antiviral medication cost per patient was the largest portion in the noncirrhotic CHC and HCV-related compensated cirrhosis cohorts. ConclusionsCHC was a costly disease in Thailand. The average annual medication cost was the largest portion in every health state, except HCV-related liver transplantation.

PP-139 Cutaneous necrosis after injection of interferon alfa-2b in a patient with HCV-related decompensated cirrhosis

PP-139 Cutaneous necrosis after injection of interferon alfa-2b in a patient with HCV-related decompensated cirrhosis