Morbidity and mortality in compensated cirrhosis type C: A retrospective follow-up study of 384 patients
Abstract
BACKGROUND & AIMS: Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C.
METHODS: A cohort of 384 European cirrhotic patients was enrolled at seven tertiary referral hospitals and followed up for a mean period of 5 years. Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B viruses and of metabolic, toxic, or autoimmune liver diseases.
RESULTS: Antibodies against hepatitis C virus were positive in 98% of 361 patients tested. The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was 18%. Death occurred in 51 patients (13%), with 70% dying of liver disease. Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred five patients (53%) were treated with interferon alfa. After adjustment for clinical and serological differences at baseline between patients treated or not treated with interferon, the 5-year estimated survival probability was 96% and 95% for treated and untreated patients, respectively.
CONCLUSIONS: In this cohort of patients, life expectancy is relatively long, in agreement with the morbidity data showing a slowly progressive disease.
(Gastroenterology 1997 Feb;112(2):463-72)
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Hepatitis C
2023, The LancetHepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.
Hepatitis C mortality trends in Mexico from 2001 to 2017
2023, Annals of HepatologyWe aimed to analyze the trends of total and sex-stratified mortality from hepatitis C virus (HCV) and to estimate the proportion of non-alcoholic liver disease deaths in Mexico attributable to HCV from 2001-2017.
Using the mortality multiple-cause dataset, we selected the codes for acute HCV and chronic HCV to analyze trends from 2001 to 2017. We then estimated the proportion of HCV-related deaths out of non-alcoholic chronic liver disease deaths, by including in the denominator: other acute and chronic viral hepatitis, malignant neoplasm of the liver, liver failure, chronic hepatitis, fibrosis, and cirrhosis of the liver, and other inflammatory diseases of the liver. Average percent change (APC) for trends, overall and by sex, were estimated using Joinpoint regression.
The trend in crude mortality rate significantly increased from 2001-2005 (APC 18.4%; 95%CI=12.5, 24.5; p value<0.001), and then significantly decreased from 2013-2017 (APC -6.5%; 95%CI=-10.1, -2.9; p value<0.001). Stratified by sex women experienced a more rapid decline in the 2014-2017 period than men.
HCV mortality seems to have started to decrease, but much remains to be done in terms of prevention, diagnosis, and timely access to treatment.
Hepatitis C: epidemiology, natural history, and diagnosis
2023, Comprehensive Guide to Hepatitis AdvancesAn estimated 71 million people have chronic hepatitis C virus (HCV) infection worldwide. Spontaneous clearance of HCV occurs in minority cases with 15%–25%, and chronic hepatitis C can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations over a 20–30 years period. Liver fibrosis generally progresses slowly but can be accelerated by host, viral, and environmental factors. Therefore, fibrosis status should be assessed by noninvasive methods regularly. The diagnosis of chronic HCV infection is based on the detection of both anti-HCV antibodies and HCV RNA. There are four main routes of HCV transmission: inject drug use, healthcare-associated transmission, mother-to-child transmission, and sexual transmission. Because of the absence of vaccine for HCV, prevention of HCV infection and reinfection is warranted to reduce the risk of HCV-related complications.
Modelling the contribution of incarceration and public health oriented drug law reform to HCV transmission and elimination among PWID in Tijuana, Mexico
2022, International Journal of Drug PolicyIncarceration is associated with increased risk of hepatitis C virus (HCV) among people who inject drugs (PWID). Mexico's previous attempt in implementing a public health-oriented drug law reform resulted in minimal impact on incarceration among PWID. However, implementation of reforms alongside Mexico's HCV elimination program has the potential to reshape the HCV epidemic among PWID in the next decade. We use data from a cohort of PWID in Tijuana, Mexico, to inform epidemic modeling to assess the contribution of incarceration and fully implemented drug reform on HCV transmission and elimination among PWID.
We developed a dynamic, deterministic model of incarceration, HCV transmission and disease progression among PWID. The model was calibrated to data from Tijuana, Mexico, with 90% HCV seroprevalence among 10,000 PWID. We estimated the 10-year population attributable fraction (PAF) of incarceration to HCV incidence among PWID and simulated, from 2022, the potential impact of the following scenarios: 1) decriminalization (80% reduction in incarceration rates); 2) fully implemented drug law reform (decriminalization and diversion to opiate agonist therapy [OAT]); 3) fully implemented drug law reform with HCV treatment (direct-acting antivirals [DAA]). We also assessed the number DAA needed to reach the 80% incidence reduction target by 2030 under these scenarios.
Projections suggest a PAF of incarceration to HCV incidence of 5.4% (95% uncertainty interval [UI]:0.6-11.9%) among PWID in Tijuana between 2022–2032. Fully implemented drug reforms could reduce HCV incidence rate by 10.6% (95%UI:3.1-19.2%) across 10 years and reduce the number of DAA required to achieve Mexico's HCV incidence reduction goal by 14.3% (95%UI:5.3-17.1%).
Among PWID in Tijuana, Mexico, incarceration remains an important contributor to HCV transmission. Full implementation of public health-oriented drug law reform could play an important role in reducing HCV incidence and improve the feasibility of reaching the HCV incidence elimination target by 2030.
Evolution of patients with chronic hepatitis C infection with advanced fibrosis or cirrhosis cured with direct-acting antivirals. Long-term follow-up
2022, Gastroenterologia y HepatologiaAnalizar la evolución analítica, clínica y de la fibrosis en pacientes F3-F4 curados con antivirales de acción directa (AAD).
Estudio unicéntrico, observacional y prospectivo. Se incluyeron todos los pacientes con hepatitis C F3-F4 curados con AAD del 1 de noviembre de 2014 al 31 de agosto de 2019. Se realizó una visita basal (VB) y a las 12 semanas (12s), 1, 2, 3 y 4 años tras finalizar el tratamiento.
Se recogieron variables demográficas, analíticas, medición no invasiva de la fibrosis, marcadores indirectos de hipertensión portal, presencia de varices esofágicas, descompensaciones de la cirrosis y hepatocarcinoma.
Se trataron 169 pacientes: 123 (72,8%) hombres, edad 57,5 ± 12 años; 117 (69,2%) presentaban cirrosis, 99 (84,6%) Child A. El 96,4% consiguieron respuesta virológica sostenida (RVS).
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El 8,1% de los pacientes con cirrosis compensada presentaron alguna descompensación. El 4,5% desarrollaron varices esofágicas.
Nueve (5,52%) pacientes presentaron hepatocarcinoma de novo; seis (3,68%) lo presentaban basalmente, y el 40% sufrieron recidiva.
Durante el seguimiento la mortalidad fue del 9,2%.
Existe mejoría de los parámetros analíticos y de la fibrosis hepática medida por métodos no invasivos en los pacientes F3-F4 curados con AAD. Sin embargo, el riesgo de descompensación y de hepatocarcinoma persiste, por lo que se debe mantener el seguimiento.
To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA).
Unicenteric, observational and prospective study. All F3–F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment.
Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected.
169 patients were treated: 123 (72.8%) men, age 57.5 ± 12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) Child A. 96,4% achieved SVR.
The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155 × 103/μL (BV); 163 × 103/μL (12w)], cholesterol [158 mg/dL (BV); 179 mg/dL (12w)] and albumin [4.16 g/dL (BV); 4.34 g/dL (12w)] and a significant decrease in ALT [82 UI/L (BV); 23 UI/L (12w], AST [69 UI/L (BV); 26 UI/L (12w)], GGT [118 UI/L (BV); 48 UI/L (12w)] and bilirrubin [0.9 mg/dL (BV); 0.7 mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9 kPa (BV); 14.8 kPa (12w; P < .05].
8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices.
Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence.
During follow-up mortality was 9.2%.
There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.
Value of Triage Treatment Strategies to Distribute Hepatitis C Direct-Acting Antiviral Agents in an Integrated Healthcare System: A Cost-Effectiveness Analysis
2022, Value in HealthThis study aimed to assess the cost-effectiveness of fibrosis-based direct-acting antiviral treatment policies for patients with chronic hepatitis C virus at the Kaiser Permanente Mid-Atlantic States health system.
We used a Markov model to compare the lifetime costs and effects of treating patients with chronic hepatitis C virus at different stages of disease severity, or all stages simultaneously, based on a fibrosis score from the US healthcare sector perspective and societal perspective. The initial distribution of patients across fibrosis scores, the effectiveness of direct-acting antiviral therapy, and follow-up and monitoring protocols were specific to the Kaiser Permanente Mid-Atlantic States health system. Direct and indirect costs, transition probabilities, and utilities were derived from the literature. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of our results.
The “Treat All” option was dominant from both the societal and healthcare sector perspectives. The conclusion was robust in deterministic sensitivity analysis. The range of incremental costs between the less restrictive policies was small—the difference between the “Treat F1+” and the “Treat All” option was only $111 per person. Probabilistic sensitivity analyses showed, at both the $100 000/quality-adjusted life-year and $150 000/quality-adjusted life-year thresholds, there was a 70% chance that the “Treat All” option was more cost-effective than the “Treat F1+” option.
We found that expanded treatment access is cost-effective and, in many cases, cost saving. Although our results are primarily applicable to a regional integrated healthcare system, it offers some direction to any healthcare setting faced with resource constraints in the face of highly priced drugs.