Role of etiological therapy in achieving recompensation of decompensated liver cirrhosis

Table 2 Efficacy of antiviral therapy in achieving recompensation of hepatitis C virus-related decompensated liver cirrhosis

Ref.	Research design, number of patients	CTP score, points	MELD score points	Hepatitis C virus genotype	Antiviral therapy	Treatment period, SVR	Main results1
Belli et al[50]	Retrospective, multicenter, N = 103	B/C	16 (6-31)	1a, 1b, 2, 3, 4	SOF, SOF/LED, SOF/DAC, SOF/SIM ± RBV	12 weeks, 98%	The median CTP score decreased from 10.0 to 8.0, and the median MELD score decreased from 15.5 to 14.0. The median serum albumin levels increased by 0.5 g/dL, the median serum total bilirubin levels decreased by 0.9 mg/dL, and the median international normalized ratio values reduced by 0.13 points. Of the entire cohort of 103 patients, 33% of liver transplant candidates were excluded from the waiting list due to clinical improvement
Foster et al[51]	Prospective, multicenter, N = 409	B/C, ≥ 7	12 (7-32)	1, 3	SOF/LED, SOF/DAC ± RBV	12 weeks, 81.6%	The MELD score decreased by an average of 0.85 points. Patients with baseline serum albumin levels < 35 g/L, sodium < 135 mmol/L, and over 65 years of age were least likely to benefit from therapy
Mandorfer et al[52]	Retrospective, single-center, N = 41	A/B	8 (7-9)	1, 2, 3, 4	SOF/DAC, SOF/LED, SOF/SIM ± RBV	12/24 weeks, 63%	The HVPG reduced by more than 10% of the baseline. The probability of HVPG reduction in CTP class B patients was lower compared with CTP class A patients
Perricone et al[53]	Prospective, cohort, N = 142	A/B/C	16 (13-18)	1a, 1b, 2, 3, 4	SOF, SOF/LED, SOF/DAC, SOF/SIM ± RBV	12 weeks, N/A	The CTP and MELD scores have improved. In 79.5% of patients, ascites was completely gone, and in 20.5% of patients it required low doses of diuretics. The hepatic encephalopathy disappeared. Within 12 weeks of starting treatment, 30.9% of liver transplant candidates were excluded from the waiting list
Macken et al[54]	Prospective, cohort, N = 39	N/A	6 (6-7)	1, 3	OMB/PAR/DAS, SOF/LED, SOF/DAC ± RBV, SOF/pegylated interferon alpha-2a/RBV	12 weeks, 77%	The recompensation was recorded in 51% of patients. The associated criterion was a lower baseline serum creatinine levels
Hanafy et al[55]	Interventional, N = 160	B/C, 11.2 ± 1.2	20.6 ± 2.04	4	SOF/DAC/RBV	12/24 weeks, 90%	There were improvements in platelet count, serum albumin levels, CTP and MELD scores, a significant reduction in the frequency of hepatic encephalopathy. Hepatocellular carcinoma developed in 10% of patients within 6.8 months ± 2.5 months after DAAs, survival was higher in the treated vs the control group
Moon et al[56]	Prospective, cohort, N = 9399	N/A	> 9 (70%)	1 (approximately 60%)	PAR/RIT/OMB/DAS, SOF ± DAC, SOF + SIM	12 weeks, 84.3%	On average, 5.1% of patients (1.66 cases per 100 patient-years) developed GEVB over a follow-up of 3.1 years. This complication was less common in patients who achieved SVR (1.55 cases per 100 patient-years) than without it (2.96 cases per 100 patient-years)
Puigvehí et al[57]	Prospective, multicenter, N = 247	A	6 (6–14)	N/A	SOF/SIM, SOF/DAC, SOF/LED ± RBV, PAR + RIT/OMB/OMB	12 weeks, 93.1%	Over a follow-up of 3 years, GEV developed in 12.5% of patients who had not had it before and increased in 33.1% of patients with low-risk GEV (< 5 mm)
Liu et al[58]	Prospective, multicenter, N = 107	B/C	10 (7–13)	1, 1a, 1b, 2, 3, 6	SOF/VEL + RBV	12 weeks, 89.7%	The CTP and MELD scores have improved in 84.4% and 64.6% of patients, respectively. The initial values of the MELD score ≥ 15 points decreased by more than 3 points
Tada et al[59]	Retrospective, multicenter, N = 65	B/C, ≥ 7	N/A	1, 2	SOF/VEL	12 weeks, 92.3%	The albumin–bilirubin score have improved during and after treatment
Tahata et al[60]	Prospective, multicenter, N = 82	A/B/C	N/A	1, 2, 3, 4	SOF/VEL	12 weeks, 90.2%	In 50% of CTP class B patients, the CTP score decreased to class A, in 27% of CTP class C patients, the CTP score decreased to class B, and in 9% of CTP class C patients, the CTP score decreased to class A. The serum albumin level increased when its initial value exceeded 28 g/L
Takaoka et al[61]	Prospective, multicenter, N = 72	B/C	9 (7-11)	1, 2	SOF/VEL	12 weeks, 95.8%	In 75% of patients who achieved SVR, there was a decrease in CTP score, and in 5.9% of patients they increased. The serum albumin levels and prothrombin time values increased, ascites decreased, while serum total bilirubin levels and the severity of hepatic encephalopathy did not change significantly
Meunier et al[62]	Retrospective, multicenter, N = 75	A/B/C	14 (11-18)	1	SOF/DAC	24 weeks, 92%	Five years after treatment, 25.3% of liver transplant candidates were excluded from the waiting list due to clinical improvement. The predictors of this were the absence of ascites, the MELD score ≤ 15 points and the CTP score ≤ 7 points
Su et al[63]	Retrospective, single-center, N = 50	B/C	12 (6–21)	1, 2, 6	SOF/DAC, SOF/LED, SOF/VEL ± RBV	12 weeks, 96%	The values of the following scores decreased: Fibrosis-4 (8.1 ± 4.0 vs 11.2 ± 6.9), CTP (6.8 ± 1.4 vs 8.0 ± 1.2), and MELD (11.6 ± 3.0 vs 12.7 ± 3.6)
Kotani et al[64]	Observational, N = 50	B/C, 8 (7–9)	10 (9–13)	1b, 2a, 2b	SOF/VEL	24 weeks, 89%	In 42% of patients who achieved SVR, the HVPG reduced by more than 20% of the baseline, and the percentage of patients with HVPG > 12 mmHg decreased from 92% to 58%. At the same time, clinically significant PH persisted in 75% of patients
Premkumar et al[65]	Prospective, cohort, N = 1152	A/B/C, 12.7 ± 1.6	16.6 (16.5 ± 4.6)	1, 2, 3 (87.1%), 4, 5, 6	SOF/DAC, SOF/VEL	12 weeks, 81.8%	The SVR resulted in recompensation in 24.7% of patients over a follow-up of 4 years. The ascites resolved in 86% of patients (diuretic withdrawal achieved in 24% of patients). Despite SVR, new hepatic decompensation evolved in 19% of patients. PH progressed in 13.7% of patients, with the development of recurrence GEVB in 4%. The hepatocellular carcinoma developed in 2.9% of patients
Yuri et al[66]	Retrospective, single-center, N = 109	A/B/C	N/A	N/A	N/A (DAAs)	24 weeks, 34,9%	At 7 years, the cumulative GEV progression rate in the DAA-SVR group was significantly lower than that in the non-SVR group. GEVB occurred in 11.3% of patients in the non-SVR group, while no GEVB events were observed in the DAA-SVR group during the observational period

¹The research results are statistically significant.

CTP: Child-Turcotte-Pugh; DAAs: Direct acting antivirals; DAC: Daclatasvir; DAS: Dasabuvir; GEV: Gastroesophageal varices; GEVB: Gastroesophageal variceal bleeding; HVPG: Hepatic venous pressure gradient; LED: Ledipasvir; N/A: Not available; MELD: Model for end stage liver disease; OMB: Ombitasvir; PAR: Paritaprevir; PH: Portal hypertension; RBV: Ribavirin; RIT: Ritonavir; SIM: Simeprevir; SOF: Sofosbuvir; SVR: Sustained virological response; VEL: Velpatasvir.