Role of etiological therapy in achieving recompensation of decompensated liver cirrhosis

Table 1 Efficacy of antiviral therapy in achieving recompensation of hepatitis B virus-related decompensated liver cirrhosis

Ref.	Research design, number of patients	CTP score, points	MELD score points	Antiviral therapy	Treatment period, SVR	Main results1
Nikolaidis et al[33]	Prospective, single-center, N = 20	B/C, 9.3 ± 2.0	16.2 ± 3.1	LAM	12-24-36 months, 55.0%	In 55% of patients, the CTP score decreased by more than 2 points, and in 45% of patients they reached CTP class A
Manolakopoulos et al[34]	Prospective, single-center, N = 19	A/B/C, 6 (5–12)	12 (7–26)	LAM	12 months, 78.9%	In 10 out of 13 patients with clinically significant portal hypertension and those who achieved SVR, there was a reduction in hepatic venous pressure gradient to less than 12 mmHg or 20% of the baseline
Shim et al[35]	Prospective, single-center, N = 55	B/C, 8.1 ± 1.7	11.5 ± 3.9	ETV	12 months, 89.1%	The CTP and MELD scores have improved. In 49% of patients, the CTP score values decreased by more than 2 points, and in 65.5% of patients they reached CTP class A
Liaw et al[36]	Randomized, open-label, comparative, N = 100, N = 91	B/C, ≥ 7, B/C, ≥ 7	17.1 (SE = 0.50), 15.3 (SE = 0.48)	ETV, ADV	12 months, 57.0%, 12 months, 20.0%	In 2/3 of the patients in both groups, the CTP score improved. The MELD score decreased by 2.6 points when treated with entecavir, and by 1.7 points when treated with adefovir
Jang et al[37]	Prospective, multicenter, N = 423	A/B/C, 8.7 ± 2.0	13.9 ± 6.4	LAM/ETV/ADV/clevudine/LdT	12 months, 57.9%	In 2/3 of the patients in both groups, the CTP score improved. The MELD score decreased by 2.6 points when treated with entecavir, and by 1.7 points when treated with adefovir
Lee et al[38]	Retrospective, multicenter, N = 57	B/C, 8.0 ± 1.5	13.4 ± 4.7	TDF	12 months, 70.2%	In 14.7% of patients, the initial values of the CTP score ≥ 7 decreased by more than 2 points, and in 12% of patients they reached CTP class A. Within 12 months of starting treatment, 33.9% of liver transplant candidates were excluded from the waiting list
Wang et al[39]	Prospective, multicenter, N = 283	B/C, 8.3 ± 1.9	13.4 ± 4.4	ETV	120 weeks, 92.2%	The CTP and MELD scores have improved. In 49.1% of patients, the initial values of the CTP score ≥ 7 decreased by more than 2 points, and in 68.4% of patients they reached CTP class A
Hui et al[40]	Retrospective, cohort, N = 1109	B, 6, 7	7.3 ± 4.5	ETV/TAF	12 months, N/A	For at least 12 months, 60.4% of patients had no ascites (off diuretics), encephalopathy (off lactulose/rifaximin) and recurrent gastroesophageal variceal bleeding. The serum albumin levels increased from 31.7 ± 6.4 to 42.4 ± 6.2, international normalized ratio values, serum levels of total bilirubin, ALT and aspartate aminotransferase decreased. The CTP and MELD scores improved: 5.77 ± 1.37 vs 8.33 ± 1.90 and 10.45 ± 4.58 vs 13.37 ± 4.44, respectively
Zhang et al[41]	Retrospective, two-center, cohort, N = 71	B/C, 8.5 ± 1.6	13.3 ± 4.3	ETV/TDF/TAF	12 months, N/A	Patients with decompensated LC who achieved recompensation showed a similar 5-year survival rate with those with compensated LC (76% and 89.3%, respectively)
Li et al[42]	Retrospective, cohort, N = 196	A/B/C	11.0 (8.0-15.0)	ETV/LAM + ADV/LdT + ADV/TDF/TAF	12 months, 78.1%	The cumulative incidence of hepatocellular carcinoma after 2 years, 4 years, and 6 years in patients with decompensated LC who achieved recompensation was the same as in those with compensated LC, which was 1.2%, 5.2%, 24.5%, and 1.3%, 5.4%, 20.0%, respectively. The rate of ascites regression was higher in SVR cohort when compared with that in non-SVR cohort. The serum ALT levels and load of serum hepatitis B virus DNA at baseline were predictors of ascites regression

¹The research results are statistically significant.

ADV: Adefovir dipivoxil; ALT: Alanine aminotransferase; CTP: Child-Turcotte-Pugh; ETV: Entecavir; LAM: Lamivudine; LC: Liver cirrhosis; LdT: Tebivudine; MELD: Model for end stage liver disease; N/A: Not available; SE: Standard error; SVR: Sustained virological response; TAF: Tenofovir alafenamide fumarate; TDF: Tenofovir disoproxil fumarate.

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.