HCV Progression in HIV Coinfection & Liver Transplantation

HCV Progression in HIV Coinfection & Liver Transplantation

Brief Summary:

This study compares 35 HIV positive and 264 negative individuals with HCV and cirrhosis for a mean time of 28 months (1-13 years). All HIV+ patients were receiving antiretroviral therapy. The study suggests HIV+ patients with cirrhosis progress more quickly to severe cirrhosis-related complications and death than HIV negative patients with cirrhosis, despite the fact that the HIV+ patients were receiving HIV treatment.

Do these findings apply to HIV+ patients receiving HAART without cirrhosis? Maybe, we don't know. Unfortunately, as with other studies there are some qualifications to this study. The HIV+ patients had significantly higher alcohol consumption, had a history of IV drug use, were more often men (women may progress less quickly) and were younger at the time of HCV infection (they may have had longer duration of HCV). The HIV+ patients had a higher death rate (47% vs 13%), and a higher incidence of cirrhosis-related complications (56% vs 19%). The patients progressed more quickly if they had HIV and if they did not receive HCV therapy. Since HIV can accelerate HCV progression, the timing of HCV therapy may be crucial. Close monitoring of disease status & progression by biopsy may be very important to prevent progression from going too far too fast.

The study authors concluded that since HCV progresses more severely in HIV+ patients access to liver transplantation may be very crucial for HIV+ patients with cirrhosis. They should have their HIV well controlled with antiretroviral therapy. At the moment HIV+ patients receive low priority for liver transplantation.

The French research group including Vincent Di Martino, Yves Benhamou and Thierry Poynard reported on the "Influence of HIV Co-Infection on the Long-Term Outcome of HCV-Related Cirrhosis". The presentation started by referring to studies showing that HIV accelerates progression to HCV related cirrhosis, and death related to cirrhosis is more frequent in HIV infected hemophiliacs. But they said there has been no follow-up cohort study in IVDUs to see what cirrhosis complications they experience and identifying other prognostic factors.

The purpose of the study is to evaluate the influence of HIV coinfection in patients with HCV-related cirrhosis on mortality and cirrhosis complications. And to assess the impact on complication from age, alcohol consumption, antiviral therapy and HIV coinfection through multivariate analysis. Data collection was retrospective and prospective. Follow-up ended with death (including cirrhosis-related death), transplantation, and date of last news. Kaplan Meier with Log-Rank and Cox were used for statistical analysis.

STUDY POPULATION

434 HBsAg (Hepatitis B) negative patients with histologically proven HCV-related cirrhosis consecutively seen between Feb 1988 and June 2000 (DOSVIRC cohort). 50 of these patients were HIV positive. 99 patients were excluded with complicated cirrhosis at the time of liver biopsy. 36 patients were excluded from analysis because they were lost to follow-up (no follow-up info after biopsy). This left 299 patients with HCV compensated cirrhosis and available follow-up data (35 HIV+). The median follow-up was 28 months, mean duration 37 months.

BASELINE PATIENT DEMOGRAPHICS (HIV+ n=35, HIV- n=264)

HIV+ patients:

were younger at the time of HCV infection 21± 6 vs 34± 14
were younger at the time of liver biopsy 39± 5 vs 53± 12
were more often IVDUs, 79% vs 18%
more often males, 91% vs 61%
had significantly higher alcohol consumption (g/day), 68± 82 vs 38± 67
All these differences were statistically significant.

There was no statistical significant differences between the HIV+ and HIV- patients in these categories (HIV+ vs HIV-):

% HCV PCR Positive (100% vs 94%),
% HCV RNA >2 million c/ml (81% vs 79%),
% HCV Genotype 1 (67% vs 57%).

ANTIRETRIVIRAL THERAPY for HIV+ Patients

29% had <200 cd4s
The average CD4 count was 320± 43
100% received antiretroviral therapy
Metavir Activity Score was not different between HIV+ & HIV- (1.79± 0.89 vs 1.71± 0.70 NS- not stat sig)

The distribution in HIV+ or HIV- by Child-Pugh scores (grading system for stage of cirrhosis) were about the same:

A5 (27 vs 247) NS
A6 (5 vs 12) NS
B7 (3 vs 5)
Albumin 39± 7 vs 40± 5 NS
Prothrombin time (%) 75± 18 vs 82± 15 (This was significant)
Bilirubin 19± 12 vs 16± 12 NS

INTERFERON+RBV TREATED PATIENTS

74% HIV+ n=26
67% HIV- NS
Median follow-up: about 28 months in both groups

COMPLICATIONS (HIV+ n=35, HIV- n=267)

The influence of HIV infection on the overall cirrhosis related complications rate at 3 years (n=11 HIV+, n=147 HIV-):

56% (HIV+) vs
19% (HIV-) (RR=2.1, 1.2-3.7).

14 of 35 HIV+ patients experienced complications of cirrhosis vs 72 of 264 HIV- patients.

	(HIV+)	(HIV-)
Death related to cirrhosis	7	42
Death not related to cirrhosis	2	3
Transplantation	0	5
Ascitis	10	43
Hepatocellular Carcinoma (cancer)	3	24
Variceal bleeding	4	18
Hepatic encepholopathy	4	16

MORTALITY RATE

At 3 years follow-up it was

47% in HIV+ patients vs
13% (p=0.02) in the HIV- patients,

a significant difference. When considering only the cirrhosis related death, it was still statistically significant:

45% (HIV+) vs
10% (HIV-) p=0.01, (RR=4.1; 2.2-7.7).

Influence of HIV infection on Ascites at 3 years

29% HIV+ vs 10% HIV-, p=0.01 (RR=2.4, 1.2-4.8).

Influence of HIV on Variceal bleeding at 3 years

20% (HIV+) vs 4% (HIV-) p=0.01, RR=2.5 (1.1-5.8)

Influence of HIV on hepatic encepholopathy & HCC

Encepholoathy: Trend but not significant (9% vs 4%) at 3 years p=0.07

HCC: 5% at 3 years for both groups, Benhamou suggested probably due to younger age of HIV+ patients. Younger age means it would take longer to progress to HCC.

Risk of Cirrhosis-related Complications was Increased when a person has HIV compared to being HIV negative, alcohol consumption >50 g/day, and if a person had not been treated with HCV therapy

MULTIVARIATE ANALYSIS: factors associated with the subsequent occurrence of cirrhosis related complications.

HIV infection (Risk Ratio: 3.4) p<0.0001
SRAC (alcohol consumption) >50g/d (RR: 2.3) p=0.02
Anti-HCV therapy (RR: 0.6) p=0.04

There is Greater Risk of Mortality by Multivariate Analysis When A person Has HIV infection (compared to being HIV negative), age >40 yrs at biopsy and if a person is not treated for HCV.

CIRRHOSIS RELATED MORTALITY: HIV infection has the highest risk ratio.

HIV Infection- (RR: 3.8; p-0.02)
Age at biopsy- >40 yrs. (RR: 1.7; p<0.001)
HCV Therapy- (RR: 0.4; p<0.001)
Not Significant by Multivariate analysis
Gender
IVDU
Metavir activity
Genotype 1
Age at HCV infection
Age at liver biopsy

This study was conducted to demonstrate the need that transplantation for people with coinfection must be considered because they are at great risk for accelerated disease progression. The transplantation community has limited access to transplants for people with HIV, but this needs to change. The authors concluded that liver transplantation should be considered in HIV+ patients with severe HCV cirrhosis when HIV is well controlled by antiretroviral therapy.