Time Of Sustained Virological Response Research Articles

Impact of Hepatitis C cure on risk of mortality and morbidity in people with HIV after ART initiation.

Hepatitis C Virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS non-liver (NANL) cancers between HCV co-infected PWH who reached SVR and mono-infected PWH. Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at time of ART initiation. Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (HR) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. Among 62,495 PWH, 2,756 acquired HCV, of whom 649 reached SVR. For 582 of these, ≥1 mono-infected PWH could be matched, producing a total of 5,062 mono-infected PWH. The estimated HRs comparing HCV co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95%CI 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared to mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV co-infected PWH who reached SVR after a DAA-based treatment compared to mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.

Real-world effectiveness and safety of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for genotype 6 chronic hepatitis C

Hepatitis C virus (HCV) genotype 6 mainly distributes in Southeast Asia and South China. Because of the low prevalence in developed countries, optimal treatment for HCV genotype 6 in real-world setting remains to be determined. We aimed to evaluate the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) for patients with HCV genotype 6 infection in Taiwan. A total of 286 patients with chronic hepatitis C (CHC) genotype 6, 161 receiving 12-week SOF/VEL and 125 receiving 8-week GLE/PIB, were enrolled. All patients were followed up for 12 weeks after treatment completion. Demographic information, HCV viral load (VL), profiles of lipid and sugar, and adverse events were recorded and reviewed. Sustained virological response (SVR) rates of SOF/VEL and GLE/PIB evaluated by intention-to-treat analysis were 99.38% and 100%, respectively. SVR achieved 100%, regardless of cirrhosis or viral load (cutoff: 6MIU/mL), of both regimens by per-protocol analysis. Skin itching was the most common adverse event, with an overall incidence of 6.64% which was more prevalent in GLE/PIB (12.0%) than SOF/VEL (2.48%). A significant decrease in the estimated glomerular filtration rate was observed in patients receiving SOF/VEL but not in those receiving GLE/PIB at the time of SVR. No patient discontinued treatment due to adverse event. The high SVR and excellent safety of SOF/VEL and GLE/PIB in real-world setting reveals that the two DAA regimens are favorable options for treatment of HCV genotype 6 in Taiwan and Asia.

Safe perioperative management of major hepatectomy in a patient with portal hypertension after elimination of hepatitis C: a case report

BackgroundThe administration of direct-acting antiviral agents in patients with liver cirrhosis and hepatitis C has been shown to improve liver function and long-term prognosis after sustained virological response (SVR) is achieved. However, in patients with portal hypertension (PH) at the time of SVR, PH may persist despite improvement in liver function.Case presentationAn 82-year-old woman with liver cirrhosis due to hepatitis C was treated with direct-acting antiviral agents and achieved SVR. During follow-up, computed tomography revealed a low-density tumor in the left lateral region of the liver with dilation of the left intrahepatic bile duct. Considering the patient’s advanced age and PH persistence with a mild decrease in liver reserve function after SVR, preoperative percutaneous transhepatic portal embolization (PTPE) and partial splenic embolization (PSE) were performed concomitantly. Laparoscopic left hemihepatectomy was performed 8 days after the PTPE and PSE. The patient was discharged 8 days after surgery without any postoperative complications.ConclusionsLaparoscopic left hemihepatectomy after preoperative management of PH was performed safely in a patient after the elimination of hepatitis C.

670Lifestyle risk factors for hepatocellular carcinoma in treated chronic hepatitis C patients

Abstract Background The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, associated with the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virological response (SVR). Methods This cross-sectional study was conducted between 2014 and 2017 using self-administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for post-SVR HCC. Results Of 202 participants, 18 had been diagnosed with post-SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95%CI, 1.08 to 83.90), and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95%CI, 1.37 to 12.46) were significantly associated with HCC. Among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with non-smokers, with marginal significance (OR, 5.61; 95%CI, 0.97 to 32.63). Conclusions In chronic hepatitis C patients with severe fibrosis, continued smoking could be a risk factor for post-SVR HCC. The relationship between gastric or duodenal ulcer history and post-SVR HCC should be investigated further. Key messages Smoking cessation may be preferred for chronic hepatitis C patients with severe fibrosis to prevent post-SVR HCC.

Delisting and clinical outcomes of liver transplant candidates after hepatitis C virus eradication: A long-term single-center experience

BackgroundPrevious short-term studies have reported on liver function improvements and delisting among liver transplantation (LT) candidates with hepatitis C virus (HCV) and decompensated liver cirrhosis after successful antiviral therapy. This study aimed to evaluate the long–term impact of HCV eradication on liver function, portal hypertension, probability of delisting, and clinical outcomes in patients awaiting LT. MethodsForty-five LT candidates with decompensated HCV cirrhosis were prospectively observed after HCV eradication by direct-acting antiviral therapy. The median follow-up (FU) time was 24 months. ResultsTwenty-six (57.8%) patients were delisted due to clinical improvement. Multivariate analysis revealed male gender (hazard ratio (HR) 3.28; p = 0.022), baseline Child – Turcotte – Pugh class C (HR 4.81; p = 0.003), and delta prothrombin index <2% between baseline and the time of sustained virological response (HR 3.82; p = 0.01) as independent risk factors for non-delisting. During a median FU of 21 months after delisting, hepatocellular carcinoma (HCC) developed in 2 (7.7%) patients. Among non-delisted patients, HCC developed in 6 (31.6%) cases, variceal bleeding developed in 3 (15.8%) patients, and spontaneous bacterial peritonitis developed in 2 (10.5%) patients. ConclusionHCV eradication lead to the delisting of more than 50% of patients, but did not eliminate the HCC risk, and close monitoring of patients should continue after the end of treatment.

Liver Stiffness-Based Strategies Predict Absence of Variceal Bleeding in Cirrhotic Hepatitis C Virus-Infected Patients With and Without Human Immunodeficiency Virus Coinfection After Sustained Virological Response.

In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Hepatocellular Carcinoma in Non-Cirrhotic Liver Patients: Is it Possible?

Cirrhosis is a major risk factor for developing HCC (hepatocellular carcinoma), therefore cirrhotic patients should still be included in surveillance HCC programs even after sustained virological response (SVR). To date, there are few studies on non-cirrhotic patients and development of HCC. A 64-year-old man with history of end-stage renal disease, diabetes mellitus type 2 and hepatitis C, treated unsuccessfully with interferon and DAA (direct acting antiviral) agent, was being evaluated for kidney transplant, and found to have new liver lesions. Laboratory work up was significant for alpha-fetoprotein (AFP) 6.2, hepatitis C ribonucleic acid (HCV RNA) 475,514 IU/mL with normal transaminases, bilirubin, albumin and INR. Computed tomography (CT) of the abdomen showed two hypodense liver lesions, more apparent on delayed imaging. First one was an ill-defined 2.4 x 1.7 cm lesion at the segment VIII, with irregular nodular enhancement. Second one was a 1.7 x 1.7cm lesion on segment IV/VII. These radiological findings were suspicious for hepatocellular carcinoma. Positron Emission Tomography (PET) CT scan showed increased uptake in the liver lesion on segment VIII. Of note, an ultrasonography of the abdomen done 6 months prior to the CT as part of surveillance for HCC was negative for hepatic lesions. Fibroscan (Transient Elastography) showed mild disease, with a reading of 6.1 kPa. Liver biopsy was consistent with mild portal inflammation/mild fibrosis and moderately differentiated hepatocellular carcinoma. Patient was referred to Interventional Radiology for Y90 radio embolization. This case illustrates that even patients with no bridging fibrosis or cirrhosis can develop HCC. This stands out from our current understanding of HCC development and its relationship with final stages of liver fibrosis. The risk of recurrent HCC after being cured is 0.33 percent per year. Therefore, patients with SVR and established cirrhosis are included in the screening HCC program. Age 65 or more, and presence of cirrhosis at the time of SVR were associated with annual HCC risk of 0.9% and 1.55%, respectively. With our case report, we raise the question that non-cirrhotic patients with chronic hepatitis C infection who were treated with DAA should be part of the screening program of HCC. Their inclusion in the program warrants prospective future trials and detailed information regarding timing and imaging studies.Figure

Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection.

The long-term prognosis in terms of risk or predictors of developing hepatocellular carcinoma (HCC) among patients with sustained virological response (SVR) remains unclear. We conducted a retrospective cohort study using data from the Veterans Affairs VA hepatitis C virus (HCV) Clinical Case Registry in patients with positive HCV RNA between October 1999 and August 2009 and follow-up through December 2010. HCV treatment (interferon with or without ribavirin) and SVR (RNA test negative at least 12 weeks after the end of treatment) were determined. We used Cox's proportional hazards models to calculate hazard ratios (HRs) for potential predictors (demographic, virological, and clinical) associated with HCC development post-SVR. We identified 33,005 HCV-infected individuals who received treatment, of whom 10,817 achieved SVR. Among these patients, 100 developed new HCC during a total follow-up of 30,562 person-years for an overall incidence rate of 0.33% per year. Annual risk of HCC remained considerably high among patients with cirrhosis (1.39%) and those cured after age 64 (0.95%). Patients with diabetes (adjusted HR = 1.88; 1.21-2.91) or genotype 3 infection (adjusted HR = 1.62; 0.96-2.734) were significantly more likely to develop HCC. Risk of HCC after HCV cure, though considerably reduced, remains relatively high at 0.33% per year. Older age and/or presence of cirrhosis at the time of SVR are associated with a high enough risk to warrant surveillance. Diabetes is also a risk factor for post-SVR HCC. (Hepatology 2016;64:130-137).