Dig Dis Sci DOI 10.1007/s10620-015-3773-y
ORIGINAL ARTICLE
Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response Jose´ Luis Casado1 • Marı´a Angeles Esteban1 • Sara Ban˜o´n1 • Ana Moreno1 • Marı´a J. Perez-Elı´as1 • Marı´a Luisa Mateos2 • Santiago Moreno1 • Carmen Quereda1
Received: 27 March 2015 / Accepted: 17 June 2015 Ó Springer Science+Business Media New York 2015
Abstract Background and Aims Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue. Methods We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR. Results Of 42 patients with SVR, 23 (55 %) had FR, in comparison with only 14 of the 91 (15 %) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/ FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p \ 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p \ 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95 % CI 0.15–0.86), and liver-related death (HR 0.15; 95 % CI 0.03–0.65), whereas both FR (HR 0.09; 95 % CI 0.03–0.3, p \ 0.01) and SVR (HR 0.24; 95 % CI 0.07–0.87) decreased the risk of liverrelated complications. & Jose´ Luis Casado [email protected] 1
Department of Infectious Diseases, Ramon y Cajal Hospital, Cra Colmenar km 9.1, 28034 Madrid, Spain
2
Department of Microbiology, Ramon y Cajal Hospital, Madrid, Spain
Conclusion Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liverrelated mortality, and liver-related complications in HIV-/ HCV-coinfected patients with cirrhosis. Keywords HIV Cirrhosis HCV Fibrosis regression Outcome Survival Liver-related complications
Introduction Liver complications due to chronic hepatitis C virus (HCV) are important causes of morbidity and mortality among HIV-infected patients. HIV coinfection accelerates HCV progression [1], and time from diagnosis of cirrhosis to death is shorter in HIV-/HCV-coinfected patients [2]. Although the use of antiretroviral therapy can reduce the rate of liver complications [3], some experts suggested that the incidence of a liver event, such as hepatocellular carcinoma (HCC), could even increase in the future [4, 5]. Nevertheless, treatment of HCV coinfection could achieve a sustained virological response (SVR). Cumulative evidence demonstrates that SVR is associated with a lower rate of complications [6–8]. However, in spite of a lower risk, patients with cirrhosis are not entirely protected against the risk of liver complications or of developing HCC after SVR [9–11]. This fact could be attributed to extensive liver fibrosis or to the persistence of liver cells committed to develop into cancer. Therefore, cirrhotic patients should remain under surveillance after SVR, as currently recommended [12, 13]. We, and others, have found an important rate of fibrosis regression (FR) during the follow-up in HIV-/HCV-coinfected patients obtaining SVR [7, 14, 15]. In hypothesis, FR after SVR should be associated with even a lower risk
123
Dig Dis Sci
of hepatic complications, and a prolonged survival. In fact, FR has also been observed in patients not achieving SVR, at least temporary, and this fact could influence the outcome of patients. Thus, to determine the impact of FR and/or SVR on the clinical outcome of cirrhosis, we conducted a study in a cohort of HIV-/HCV-coinfected patients with cirrhosis, who received pegylated IFN and ribavirine, with the aim of evaluating the benefit of fibrosis improvement on survival and on the risk to develop liver complications.
value of 12.5 kilopascals (kPa), which had a positive and negative predictive value of 77 and 95 %, respectively. We also determined serum alpha-fetoprotein (AFP) concentration during follow-up. The following clinical events were classified as liverrelated complications: portal hypertensive gastrointestinal bleeding, ascites, hepatic encephalopathy, and hepatocellular carcinoma (HCC). All diagnoses were confirmed by a systematic search of the hospital and local authorities registry, which received and centralized data about date and cause of death and diagnosis at the time of.
Methods
Definitions
This observational cohort study was composed of patients treated with pegylated interferon and ribavirin and was established in 2006 to follow up by transient elastography (TE) patients coinfected with HIV/HCV who received therapy with these drugs at our unit since 2004. For the purpose of this study, we include those patients with cirrhosis in the baseline fibrosis determination by liver biopsy or by TE, who had at least one determination of liver fibrosis by TE after therapy. All patients treated received peg-IFN alfa 2a or 2b plus weight-adjusted ribavirin according to Spanish consensus. Patients who had a prior history of liver complications at inclusion (four patients with previous gastrointestinal bleeding) were also included, but patients already in liver transplant waiting list were excluded. The study was approved by our IRB (EC 150/06), and patients signed written informed consent. Variables collected include age, sex, baseline and nadir CD4? cell counts and baseline viral load HIV, information about highly active antiretroviral therapy (HAART), and information related to HCV infection (time of HCV infection, baseline HCV RNA, HCV genotype). HCV RNA tests both quantitative and qualitative were performed with commercial assays, first Amplicor HCV test (Roche Diagnostics, Mannheim, Germany, sensitivity of 50 IU/ml) and after 2008, with Roche Ampliprep/Cobas Taqman test (detection limit 15 IU/ml). We also assessed AST-platelet ratio index (APRI) as APRI = AST ([upper limit of normal) 9 100/platelet count (109/l). For biopsy samples, an experienced pathologist analyzed liver biopsy samples obtaining the histological activity index (HAI), and a staging of fibrosis according to the modified Knodell scoring system [16]. Hepatic transient elastography (FibroScan; Echosens, Paris, France) was carried out at inclusion and during follow-up, according to a standardized technique by one experienced operator. Liver fibrosis stages were correlated with stiffness according to cutoff criteria by Castera et al. [17], and therefore fibrosis grade 4 or cirrhosis was established according to a liver stiffness measurement (LSM) cutoff
SVR was defined as undetectable HCV RNA using PCR assay 24 weeks after the end of treatment. Fibrosis regression was defined as a reduction in fibrosis in the first TE during the follow-up (TE without cirrhosis), without worsening in successive TE, if available. Ascites was diagnosed by clinical examination and/or ultrasound detection. Portosystemic encephalopathy was defined by clinical parameters. The source of gastroesophageal bleeding was confirmed by endoscopy in all cases. The diagnosis of HCC was confirmed on the basis of a verified focal liver lesion by imaging techniques [5, 13].
123
Main Outcome Measure The primary endpoints were death from any cause and liverrelated death. The secondary endpoint was the development of a liver-related complication. The time to the event was the length of time since end of antiviral therapy until the primary endpoint. Liver transplantation was considered as a liverrelated endpoint. For patients who did not die or were not transplanted, the analysis was censored at July 2014. The incidence of liver-related complications, liver-related death, and overall death in relation to SVR and FR status was estimated as the number of events occurring at each category divided by the corresponding person-time at risk in the category. Follow time at risk was divided into four categories: SVR/fibrosis regression (FR), SVR/no FR, non-SVR/FR, and non-SVR/no FR. Statistical Analysis Continuous variables were compared using the Student t test or Mann–Whitney U test, depending on the normality of distributions. Categorical variables were compared using the Chi-square test or the Fisher’s test, when appropriate. Differences in continuous related variables (i.e., changes in alpha-fetoprotein) were compared by Wilcoxon rank test. Cumulative incidence curves of liver-related complications and liver mortality according to response and fibrosis
Dig Dis Sci
regression were plotted using the Kaplan–Meier method. The differences between groups were assessed using logrank tests. A multivariate Cox model was used to assess the independent effect of variables on the development of events during the follow-up. The results were expressed as hazard ratio (HR) and their 95 % confidence interval (CI). All tests were two-sided, and a p value \0.05 was considered to be statistically significant.
Results Between October 2004 and December 2011, 139 patients with a baseline fibrosis 4 received anti-HCV therapy. Six patients without SVR died before 3 months of follow-up, and LSM could not be performed after therapy and were not included in the study. Baseline characteristics of the remaining 133 patients are shown in the Table 1. Liver biopsy had been performed in 92 cases (69 %), a median time of 165 days (43–1043) before therapy. All the patients had fibrosis 4, and the median histological activity index (HAI) was 5.84 (4–12). The remaining 41 patients had a LSM before therapy confirming fibrosis 4.
SVR and/or Fibrosis Regression Overall, 53 % patients reached early virological response (EVR), 38 % achieved virological response at the end of therapy (ETVR), and 42 patients (32 %) achieved SVR. As shown in the Table 1, only HCV genotype and, as it could be expected, a higher time on IFN therapy were associated with SVR. Of note, SVR patients had lower levels of serum AFP, and a trend to lower LSM, suggesting a less advanced fibrosis. During follow-up, all patients had a LSM in a median time of 491 days (IQR 255–1831) after therapy, showing a median stiffness value of 16.35 kPa (3.9–73.5): All the 41 patients with baseline LSM had improvement, 96 patients (72 %) remained with fibrosis 4 (Table 2), and 37 patients (28 %) had fibrosis improvement showing fibrosis 3, 2, and 1 in 9, 12, and 16 patients, respectively (28 patients, 21 % had C2 points reduction in Metavir score). In a second LSM, performed in a median of 969 days after therapy (461–3117) in 115 patients (24 died), median stiffness value was 14.95 (3.5–75), and 53 % of patients remained with fibrosis 4. Of note, 70 out of these 115 had an additional LSM decrease in comparison with the first TE (median decrease -1.3; IQR -4, ?3.7).
Table 1 Baseline characteristics of 133 HIV/HCV cirrhotic patients according to response to interferon plus ribavirin therapy Variable
Overall (n = 133)
SVR (n = 42, 32 %)
Non-SVR (n = 91, 68 %)
p value
Mean age (years)
41.7 (39–44)
41.9 (38–46)
41.6 (39–43.7)
0.7
Sex male, n (%)
108 (81 %)
32 (76 %)
76 (84 %)
0.77
Previous AIDS diagnosis
44 (33 %)
11 (26 %)
33 (36 %)
0.6
Nadir CD4? count (cells/mm3)
137 (70–254)
157 (93–260)
129 (68–252)
0.64
121 (91 %)
36 (86 %)
85 (93 %)
0.4
Baseline CD4 count (cells/mm )
440 (256–624)
432 (279–561)
440 (255–670)
0.76
Baseline HIV RNA level \50 copies/ml
99 (82 %)
32 (89 %) %
67 (79 %)
0.2
Time of HCV infection (years)
22 (8–36)
22.3 (18–26.7)
21.7 (19–24)
0.54
1
79 (59 %)
14 (34 %)
65 (71 %)
2 3
3 (2 %) 34 (26 %)
2 (5 %) 19 (46 %)
1 (1 %) 15 (16 %)
4
On stable HAART ?
3
\0.01
HCV viral genotype
23 (17 %)
7 (17 %)
16 (18 %)
RNA HCV (log, UI/ml)
5.9 (5.6–6.2)
6 (5.1–6.4)
5.9 (5.3–61)
0.7
Alpha-fetoprotein
9 (4–21.4)
5.03 (2.3–9)
11 (4.4–24.5)
\0.01
HAIa
5.84 (4–12)
4.88 (1.5–7.5)
6.09 (5–8)
Baseline LSMb
22.4 (16.5–73)
19 (17.2–71)
29.3 (16.5–73)
0.1
APRI score
2.52 (1.45–3.96)
2.41 (1.1–3.9)
2.61 (1.5–6.5)
0.32 \0.01
Time of anti-HCV therapy (days)
268 (173–343)
336 (228–369)
238 (146–330)
Time of follow-up after therapy (days)
2448 (1392–3474)
2254 (1765–3188)
2691 (1345–3515)
0.15
0.61
Values are expressed as median and interquartile range (IQR), unless otherwise specified Bold values indicate statistically significant differences between groups SVR sustained virological response, HAI histological activity index, APRI AST-to-platelet index, LSM liver stiffness measurement a Available only for 92 patients b
Available for 41 patients
123
Dig Dis Sci Table 2 Baseline characteristics of the patients according to response to IFN therapy and fibrosis regression SVR (42) FR (23, 55 %)
Non-SVR (91) No FR (19, 45 %)
p value
FR (14, 15 %)
No FR (77, 85 %)
p value
Mean age (years)
40.7
43.4
0.2
43.3
41.2
0.05
Sex male, n (%)
18 (78 %)
14 (74 %)
0.8
78 %
61 (79 %)
0.9
Nadir CD4? count (cells/mm3)
191 (129–291)
124 (64–229)
0.2
104 (48–249)
133 (70–250)
0.52
Baseline CD4 count (cells/mm )
364 (292–544)
461 (238–713)
0.5
489 (129–910)
434 (255–631)
0.56
Baseline HIV RNA level \50 copies/ml (on TAR)
18/20
14/17
0.6
13/14
66/77
0.7
Time of HCV infection (years)
19.5 (17.2–24.5)
23.5 (19–27)
0.14
24 (20–27)
21 (19–24)
0.05
?
3
HCV genotype
0.1
0.01
1
5 (22 %)
9 (47 %)
11 (79 %)
53 (58 %)
2
2 (9 %)
0
1 (7 %)
0
3
12 (52 %)
7 (37 %)
1 (7 %)
14 (15 %)
4
4 (17 %)
3 (16 %)
1 (7 %)
10 (11 %)
RNA HCV (log IU/ml)
6 (5.3–6.4)
5.9 (3.7–7.9)
0.4
5.7 (5.6–6)
5.9 (5.6–6.2)
Baseline AFP
3.6 (2.12–7.75)
8 (2.82–15.5)
0.17
7 (4.8–21.5)
11 (4.2–24)
0.4
HAIa
4 (1–6)
7.5 (5.2–8.5)
0.05
5 (4.5–7.5)
6 (5–8)
0.3
0.55
Baseline LSM
24.1 (16.2–49)
29 (18–55)
0.1
32.1 (14.5–61)
36.9 (19–73)
0.11
APRI score
2.19 (1–4.2)
2.46 (1.45–3.61)
0.64
1.52 (0.68–2.6)
3.1 (1.8–4.4)
ORIGINAL ARTICLE
Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response Jose´ Luis Casado1 • Marı´a Angeles Esteban1 • Sara Ban˜o´n1 • Ana Moreno1 • Marı´a J. Perez-Elı´as1 • Marı´a Luisa Mateos2 • Santiago Moreno1 • Carmen Quereda1
Received: 27 March 2015 / Accepted: 17 June 2015 Ó Springer Science+Business Media New York 2015
Abstract Background and Aims Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue. Methods We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR. Results Of 42 patients with SVR, 23 (55 %) had FR, in comparison with only 14 of the 91 (15 %) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/ FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p \ 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p \ 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95 % CI 0.15–0.86), and liver-related death (HR 0.15; 95 % CI 0.03–0.65), whereas both FR (HR 0.09; 95 % CI 0.03–0.3, p \ 0.01) and SVR (HR 0.24; 95 % CI 0.07–0.87) decreased the risk of liverrelated complications. & Jose´ Luis Casado [email protected] 1
Department of Infectious Diseases, Ramon y Cajal Hospital, Cra Colmenar km 9.1, 28034 Madrid, Spain
2
Department of Microbiology, Ramon y Cajal Hospital, Madrid, Spain
Conclusion Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liverrelated mortality, and liver-related complications in HIV-/ HCV-coinfected patients with cirrhosis. Keywords HIV Cirrhosis HCV Fibrosis regression Outcome Survival Liver-related complications
Introduction Liver complications due to chronic hepatitis C virus (HCV) are important causes of morbidity and mortality among HIV-infected patients. HIV coinfection accelerates HCV progression [1], and time from diagnosis of cirrhosis to death is shorter in HIV-/HCV-coinfected patients [2]. Although the use of antiretroviral therapy can reduce the rate of liver complications [3], some experts suggested that the incidence of a liver event, such as hepatocellular carcinoma (HCC), could even increase in the future [4, 5]. Nevertheless, treatment of HCV coinfection could achieve a sustained virological response (SVR). Cumulative evidence demonstrates that SVR is associated with a lower rate of complications [6–8]. However, in spite of a lower risk, patients with cirrhosis are not entirely protected against the risk of liver complications or of developing HCC after SVR [9–11]. This fact could be attributed to extensive liver fibrosis or to the persistence of liver cells committed to develop into cancer. Therefore, cirrhotic patients should remain under surveillance after SVR, as currently recommended [12, 13]. We, and others, have found an important rate of fibrosis regression (FR) during the follow-up in HIV-/HCV-coinfected patients obtaining SVR [7, 14, 15]. In hypothesis, FR after SVR should be associated with even a lower risk
123
Dig Dis Sci
of hepatic complications, and a prolonged survival. In fact, FR has also been observed in patients not achieving SVR, at least temporary, and this fact could influence the outcome of patients. Thus, to determine the impact of FR and/or SVR on the clinical outcome of cirrhosis, we conducted a study in a cohort of HIV-/HCV-coinfected patients with cirrhosis, who received pegylated IFN and ribavirine, with the aim of evaluating the benefit of fibrosis improvement on survival and on the risk to develop liver complications.
value of 12.5 kilopascals (kPa), which had a positive and negative predictive value of 77 and 95 %, respectively. We also determined serum alpha-fetoprotein (AFP) concentration during follow-up. The following clinical events were classified as liverrelated complications: portal hypertensive gastrointestinal bleeding, ascites, hepatic encephalopathy, and hepatocellular carcinoma (HCC). All diagnoses were confirmed by a systematic search of the hospital and local authorities registry, which received and centralized data about date and cause of death and diagnosis at the time of.
Methods
Definitions
This observational cohort study was composed of patients treated with pegylated interferon and ribavirin and was established in 2006 to follow up by transient elastography (TE) patients coinfected with HIV/HCV who received therapy with these drugs at our unit since 2004. For the purpose of this study, we include those patients with cirrhosis in the baseline fibrosis determination by liver biopsy or by TE, who had at least one determination of liver fibrosis by TE after therapy. All patients treated received peg-IFN alfa 2a or 2b plus weight-adjusted ribavirin according to Spanish consensus. Patients who had a prior history of liver complications at inclusion (four patients with previous gastrointestinal bleeding) were also included, but patients already in liver transplant waiting list were excluded. The study was approved by our IRB (EC 150/06), and patients signed written informed consent. Variables collected include age, sex, baseline and nadir CD4? cell counts and baseline viral load HIV, information about highly active antiretroviral therapy (HAART), and information related to HCV infection (time of HCV infection, baseline HCV RNA, HCV genotype). HCV RNA tests both quantitative and qualitative were performed with commercial assays, first Amplicor HCV test (Roche Diagnostics, Mannheim, Germany, sensitivity of 50 IU/ml) and after 2008, with Roche Ampliprep/Cobas Taqman test (detection limit 15 IU/ml). We also assessed AST-platelet ratio index (APRI) as APRI = AST ([upper limit of normal) 9 100/platelet count (109/l). For biopsy samples, an experienced pathologist analyzed liver biopsy samples obtaining the histological activity index (HAI), and a staging of fibrosis according to the modified Knodell scoring system [16]. Hepatic transient elastography (FibroScan; Echosens, Paris, France) was carried out at inclusion and during follow-up, according to a standardized technique by one experienced operator. Liver fibrosis stages were correlated with stiffness according to cutoff criteria by Castera et al. [17], and therefore fibrosis grade 4 or cirrhosis was established according to a liver stiffness measurement (LSM) cutoff
SVR was defined as undetectable HCV RNA using PCR assay 24 weeks after the end of treatment. Fibrosis regression was defined as a reduction in fibrosis in the first TE during the follow-up (TE without cirrhosis), without worsening in successive TE, if available. Ascites was diagnosed by clinical examination and/or ultrasound detection. Portosystemic encephalopathy was defined by clinical parameters. The source of gastroesophageal bleeding was confirmed by endoscopy in all cases. The diagnosis of HCC was confirmed on the basis of a verified focal liver lesion by imaging techniques [5, 13].
123
Main Outcome Measure The primary endpoints were death from any cause and liverrelated death. The secondary endpoint was the development of a liver-related complication. The time to the event was the length of time since end of antiviral therapy until the primary endpoint. Liver transplantation was considered as a liverrelated endpoint. For patients who did not die or were not transplanted, the analysis was censored at July 2014. The incidence of liver-related complications, liver-related death, and overall death in relation to SVR and FR status was estimated as the number of events occurring at each category divided by the corresponding person-time at risk in the category. Follow time at risk was divided into four categories: SVR/fibrosis regression (FR), SVR/no FR, non-SVR/FR, and non-SVR/no FR. Statistical Analysis Continuous variables were compared using the Student t test or Mann–Whitney U test, depending on the normality of distributions. Categorical variables were compared using the Chi-square test or the Fisher’s test, when appropriate. Differences in continuous related variables (i.e., changes in alpha-fetoprotein) were compared by Wilcoxon rank test. Cumulative incidence curves of liver-related complications and liver mortality according to response and fibrosis
Dig Dis Sci
regression were plotted using the Kaplan–Meier method. The differences between groups were assessed using logrank tests. A multivariate Cox model was used to assess the independent effect of variables on the development of events during the follow-up. The results were expressed as hazard ratio (HR) and their 95 % confidence interval (CI). All tests were two-sided, and a p value \0.05 was considered to be statistically significant.
Results Between October 2004 and December 2011, 139 patients with a baseline fibrosis 4 received anti-HCV therapy. Six patients without SVR died before 3 months of follow-up, and LSM could not be performed after therapy and were not included in the study. Baseline characteristics of the remaining 133 patients are shown in the Table 1. Liver biopsy had been performed in 92 cases (69 %), a median time of 165 days (43–1043) before therapy. All the patients had fibrosis 4, and the median histological activity index (HAI) was 5.84 (4–12). The remaining 41 patients had a LSM before therapy confirming fibrosis 4.
SVR and/or Fibrosis Regression Overall, 53 % patients reached early virological response (EVR), 38 % achieved virological response at the end of therapy (ETVR), and 42 patients (32 %) achieved SVR. As shown in the Table 1, only HCV genotype and, as it could be expected, a higher time on IFN therapy were associated with SVR. Of note, SVR patients had lower levels of serum AFP, and a trend to lower LSM, suggesting a less advanced fibrosis. During follow-up, all patients had a LSM in a median time of 491 days (IQR 255–1831) after therapy, showing a median stiffness value of 16.35 kPa (3.9–73.5): All the 41 patients with baseline LSM had improvement, 96 patients (72 %) remained with fibrosis 4 (Table 2), and 37 patients (28 %) had fibrosis improvement showing fibrosis 3, 2, and 1 in 9, 12, and 16 patients, respectively (28 patients, 21 % had C2 points reduction in Metavir score). In a second LSM, performed in a median of 969 days after therapy (461–3117) in 115 patients (24 died), median stiffness value was 14.95 (3.5–75), and 53 % of patients remained with fibrosis 4. Of note, 70 out of these 115 had an additional LSM decrease in comparison with the first TE (median decrease -1.3; IQR -4, ?3.7).
Table 1 Baseline characteristics of 133 HIV/HCV cirrhotic patients according to response to interferon plus ribavirin therapy Variable
Overall (n = 133)
SVR (n = 42, 32 %)
Non-SVR (n = 91, 68 %)
p value
Mean age (years)
41.7 (39–44)
41.9 (38–46)
41.6 (39–43.7)
0.7
Sex male, n (%)
108 (81 %)
32 (76 %)
76 (84 %)
0.77
Previous AIDS diagnosis
44 (33 %)
11 (26 %)
33 (36 %)
0.6
Nadir CD4? count (cells/mm3)
137 (70–254)
157 (93–260)
129 (68–252)
0.64
121 (91 %)
36 (86 %)
85 (93 %)
0.4
Baseline CD4 count (cells/mm )
440 (256–624)
432 (279–561)
440 (255–670)
0.76
Baseline HIV RNA level \50 copies/ml
99 (82 %)
32 (89 %) %
67 (79 %)
0.2
Time of HCV infection (years)
22 (8–36)
22.3 (18–26.7)
21.7 (19–24)
0.54
1
79 (59 %)
14 (34 %)
65 (71 %)
2 3
3 (2 %) 34 (26 %)
2 (5 %) 19 (46 %)
1 (1 %) 15 (16 %)
4
On stable HAART ?
3
\0.01
HCV viral genotype
23 (17 %)
7 (17 %)
16 (18 %)
RNA HCV (log, UI/ml)
5.9 (5.6–6.2)
6 (5.1–6.4)
5.9 (5.3–61)
0.7
Alpha-fetoprotein
9 (4–21.4)
5.03 (2.3–9)
11 (4.4–24.5)
\0.01
HAIa
5.84 (4–12)
4.88 (1.5–7.5)
6.09 (5–8)
Baseline LSMb
22.4 (16.5–73)
19 (17.2–71)
29.3 (16.5–73)
0.1
APRI score
2.52 (1.45–3.96)
2.41 (1.1–3.9)
2.61 (1.5–6.5)
0.32 \0.01
Time of anti-HCV therapy (days)
268 (173–343)
336 (228–369)
238 (146–330)
Time of follow-up after therapy (days)
2448 (1392–3474)
2254 (1765–3188)
2691 (1345–3515)
0.15
0.61
Values are expressed as median and interquartile range (IQR), unless otherwise specified Bold values indicate statistically significant differences between groups SVR sustained virological response, HAI histological activity index, APRI AST-to-platelet index, LSM liver stiffness measurement a Available only for 92 patients b
Available for 41 patients
123
Dig Dis Sci Table 2 Baseline characteristics of the patients according to response to IFN therapy and fibrosis regression SVR (42) FR (23, 55 %)
Non-SVR (91) No FR (19, 45 %)
p value
FR (14, 15 %)
No FR (77, 85 %)
p value
Mean age (years)
40.7
43.4
0.2
43.3
41.2
0.05
Sex male, n (%)
18 (78 %)
14 (74 %)
0.8
78 %
61 (79 %)
0.9
Nadir CD4? count (cells/mm3)
191 (129–291)
124 (64–229)
0.2
104 (48–249)
133 (70–250)
0.52
Baseline CD4 count (cells/mm )
364 (292–544)
461 (238–713)
0.5
489 (129–910)
434 (255–631)
0.56
Baseline HIV RNA level \50 copies/ml (on TAR)
18/20
14/17
0.6
13/14
66/77
0.7
Time of HCV infection (years)
19.5 (17.2–24.5)
23.5 (19–27)
0.14
24 (20–27)
21 (19–24)
0.05
?
3
HCV genotype
0.1
0.01
1
5 (22 %)
9 (47 %)
11 (79 %)
53 (58 %)
2
2 (9 %)
0
1 (7 %)
0
3
12 (52 %)
7 (37 %)
1 (7 %)
14 (15 %)
4
4 (17 %)
3 (16 %)
1 (7 %)
10 (11 %)
RNA HCV (log IU/ml)
6 (5.3–6.4)
5.9 (3.7–7.9)
0.4
5.7 (5.6–6)
5.9 (5.6–6.2)
Baseline AFP
3.6 (2.12–7.75)
8 (2.82–15.5)
0.17
7 (4.8–21.5)
11 (4.2–24)
0.4
HAIa
4 (1–6)
7.5 (5.2–8.5)
0.05
5 (4.5–7.5)
6 (5–8)
0.3
0.55
Baseline LSM
24.1 (16.2–49)
29 (18–55)
0.1
32.1 (14.5–61)
36.9 (19–73)
0.11
APRI score
2.19 (1–4.2)
2.46 (1.45–3.61)
0.64
1.52 (0.68–2.6)
3.1 (1.8–4.4)
