Treatment of hepatitis C has long relied on the ribavirin/interferon/pegyl combination, with only 45% of patients achieving a sustained viral response; this rate is lower in patients with cirrhosis [1] . Direct Acting Antivirals (DAA) have improved sustained viral response, prevented cirrhosis-related complications in compensated patients, and enhanced the CHILD score in patients with advanced Child scores [1] . In cirrhotic patients, the advantage of antivirals lies in their tolerability and efficacy compared with conventional treatments, enabling, in some cases, regression of fibrosis [2] .

Our work mainly aims to compare the therapeutic response of patients with post-viral cirrhosis C on DAA with those on ribavirin or pegylated interferon and overall survival in patients with the two treatment regimens.

Between January 2009 and January 2024, we enrolled 105 cirrhotic patients.

The hepatitis C virus is genetically highly heterogeneous and can be classified into eight significant genotypes, which are themselves subdivided into more than 70 subtypes. Their distribution varies worldwide, with genotype one being the most frequently encountered in our regions, followed by genotype 2 [3] . Among patients with chronic hepatitis C, 15% to 20% will have advanced disease, normal

transaminase levels, and minimal histological lesions. In comparison, 60% will have a disturbance of the liver balance associated with significant inflammation and progressive fibrosis observed on liver biopsy, and 20% of the latter will suffer cirrhosis twenty years later [4] .

Pre-therapeutic assessment of liver disease is essential, as it conditions the patient’s prognosis and modifies his or her management. The initial work-up should investigate all other causes of chronic liver disease (alcohol, metabolic syndrome, HBV, hemochromatosis, autoimmune hepatitis, chronic cholestatic diseases, etc.). In our series, the comorbidities found in our patients were diabetes in 9 patients, heart disease in 6 patients, obesity in 5 patients (3.08%), metabolic syndrome in 3 patients (1.85%), renal insufficiency in 12%, with 1 case of HBV-HCV association and another of HBV-HIV association. 8.6% were chronic alcoholics.

Biologically, 12% had kidney failure, 11 of whom were already on hemodialysis, which is in line with the literature or HCV infection is frequent in patients with renal failure, mainly hemodialysis patients, with a prevalence varying between 10 and 65% depending on the geographical area [5] . Anemia was also noted in 12.34% of cirrhotic patients, and thrombocytopenia was present in 44.44%.

Treatment of hepatitis C-linked cirrhosis was initially limited to interferon-alpha monotherapy, but less than 20% of patients achieved a sustained virological response. Until 2002, it was based on combining two molecules: Pegylated interferon-alpha and Ribavirin, which considerably increased the sustained virological response, although this did not exceed 40% to 50% [5] . In our study, 60 patients were initially treated with previous hepatitis C therapies (pegylated therapy). Pegylated interferon is administered subcutaneously once a week at a fixed dose for α-2a (180 μg/week) or adapted to weight for α-2b (1.5 μg/kg/week). Ribavirin is administered per os at a weight-adjusted dose (1000 mg/d if < 75 kg or 1200 mg/d if > 75 kg). This combination is prescribed for 24 to 48 weeks, depending on viral genotype and virological response to treatment. The results were unsatisfactory: SVR was achieved in 59 cases (55.14%), treatment failure was noted in 14 (13.1%), and relapse was observed in 14 cases, which is in line with the data in the literature, such as the French survey carried out in 2010 [6] , which revealed the following results: 34.5% of patients were virological non-responders, 19% responder-relapsers, and only 46.5% sustained virological response, as well as the EPIC 2010 survey [7] .

A retrospective multicenter study carried out in 28 French departments of internal medicine, hepato-gastroenterology, and infectious diseases reported the results of antiviral treatment in real life: 41.3% patients were virologically non-responders, 28.1% responder-rejecters, and only 30.7% sustained virological response [8] .

On the other hand, significant side effects were observed, altering patients’ quality of life. Our results are similar to those reported in the literature, where the side effects observed with pegylated interferon and ribavirin therapy were headache 47% - 62%, fever 40% - 46%, myalgia 37-56%, arthralgia 24% - 34%, nausea 35% - 43%, anorexia 21%, diarrhea 22%, alopecia 21% - 36%, rash 20% - 24%, asthenia 48% - 64%, sleep disturbance 33% - 40%, irritability 24% - 35% and depression 22% - 31%. Dose reduction or discontinuation of treatment for adverse effects was noted in our series, respectively, in 40.48% and 5.60% of cases, compared with 42% and 14% in the international literature [9] [10] .

New, highly effective, well-tolerated molecules from the DAA class came to market in 2014. These treatments do away with the need for interferon, responsible for numerous side effects. The cure rate in less than six months of well-monitored therapy, regardless of HCV genotype, is over 90% [11] . The most frequently proposed regimens were sofosbuvir SOF/Daclatasvir (DAC) ± RBV in 85.45% of patients, followed by (SOF)/ledipasvir (LDV)±ribavirin (RBV). The treatment duration was 12 weeks in most cases. A sustained virological response at 12 weeks after the end of treatment was noted in 98.18% of patients with failure in a single cirrhotic patient pre-treated with pegylated dual therapy. Our data concur with those of the ANRS CO 22 HEPATHER cohort of 9895 patients recruited from 32 centers in France, where DAAs were able to eliminate the virus in almost all treated patients (95% overall) [12] . A meta-analysis of 19 studies by Prazzol et al. involving a total of 57,433 people concluded that SVR was 98%, which is in line with the results of our study [13] .

In our study, tolerance to DAAs was excellent in all cases, with only 9% of patients reporting minor adverse events that did not lead to treatment discontinuation. The only discontinuation of DAAs due to hepatic encephalopathy with ascites fluid infection was in a decompensated cirrhotic patient. The main adverse events were asthenia (n = 2), joint pain or myalgia (n = 2), and vomiting in only one case, which is in line with data in the literature, such as that of Marbet et al. where tolerance was excellent, with no need to discontinue treatment in any case [14] . In addition, the mortality rate was significantly lower in HCC patients on DAAs (p < 0.001).

Thus, our results concur with those of a French study including 9895 patients over an average duration of 33 months with 7344 patients on DAA. This treatment was associated with a lower rate of mortality and HCC. Indeed, after adjusting for individual factors (age, stage of disease, presence of other pathologies), patients treated with DAAs had a 52% lower risk of mortality and a 33% lower risk of developing liver cancer than patients with a similar stage of disease but not taking DAAs [14] .

Since the discovery of the hepatitis C virus, various molecules interfering with specific stages of the viral cycle have been developed to slow the development of the disease. The therapeutic efficacy of recent treatments, essentially DAA, is to raise hopes of eradicating the virus soon. Our study also demonstrated the superiority of DAAs in terms of efficacy and tolerability compared with older treatments for CVH and a reduction in hepatic complications. However, it should be noted that effective treatment is not enough to eradicate the virus by 2030, as the WHO envisages; there is still a long way to go. We need to encourage screening, which is a good way of combating hepatitis C.

DAA: Direct-acting antivirals

DAC: Daclatasvir

HCC: Hepatocellular carcinoma

LDV: Lédipasvir

RBV: Ribavirine

SVR: Sustained viral response

VHC: Viral hepatitis C

VHB: Viral hepatitis B